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Purpose. To develop a mathematical approach to quantitative assessment of the effectiveness of digital marketing of territories. To determine the tasks of digital marketing of territories and directions for increasing its effectiveness. Methodology. The research uses general and special methods of cognition: content analysis to substantiate the use of quantitative indicators for evaluating marketing effectiveness; induction and deduction for the development of a mathematical approach to evaluating the effectiveness of digital marketing of territories; analysis and synthesis to coordinate projects under conditions of a dynamic transformation of marketing processes. Findings. The mathematical formalization of quantitative evaluation effectiveness of marketing territories is developed, provided that the possibility of implementing project approach and conditions for coordination of projects is ensured. The tasks to be solved by the digital marketing of territories and directions for increasing its effectiveness are defined, and its advantages are detailed. The scheme is proposed for the implementation of territory marketing, taking into account the direct impact of information tools on the result and the reverse impact of an inappropriate result on the choice of information tools, which dictates the need to ensure the adaptability of marketing to dynamic changes in external and internal influences. Originality. The synergistic mutual influence of territory marketing and digital technologies, the synergistic mutual influence of business activities in the territorial location and the marketing of territories is established. It is established that the factor that determines the dynamic change in marketing plans is also a significant level of uncertainty due to the dynamic change in the level of threats and the dynamic nature of the introduction of the latest technologies. Practical value. The mathematical approach of quantitative assessment effectiveness of digital marketing territories and the determination of its tasks and directions for increasing efficiency determine the practical value of the study.

Purpose. To propose measures on assessing the initial state of the environment based on the foreign experience of natural resources protection by business structures in the extractive industry (using the example of some countries that are members of the Organization for Economic Co-operation and Development (OECD). Methodology. In the course of the scientific research, the authors used a number of general scientific and special methods of cognition, such as analysis for critical assessment of approaches to the interpretation of the essence and necessity of nature protection; quantitative and qualitative comparisons to highlight the mutual impact of environmental protection measures used by companies of OECD member countries; scientific abstraction and systematization for setting out proposals regarding the application of the most successful measures for Ukraine, applied by OECD member countries. Findings. The authors considered the experience of foreign member countries of the OECD such as Kazakhstan, Australia, Canada, the USA in terms of the implementation of some international regulations on labor protection, local maintenance standards, the governments focus on cooperation with license holders for subsoil use operations. Originality. The authors suggested that the government of Ukraine pay attention to the measures introduced by Australia in terms of assessment of the initial state of the environment. Subsoil user companies should collect environmental information at the project planning stage in order to determine the factors that are subject to monitoring, further study, and control at the stage of liquidation of consequences after the termination of operations. Environmental information should include information on climatic conditions, geological data, soil data, hydrological data, data on vegetation, terrestrial and subterranean fauna, as well as information on socioeconomic conditions and cultural heritage sites. Practical value. The considered experience is also useful for Ukraine, since we have a significant part of enterprises in the extractive industry and the issues of environmental protection and nature management should occupy one of the first places in companies. The results of the research can be used by practitioners, scientists, and civil servants for further perspectives of the development.

Purpose. To study the impact of quarantine restrictions on the financial and economic performance of business structures. Methodology. Both general and special methods of cognition were used in the study: system analysis, structural and functional method, comparison, synthesis, deduction, logical research, graphical way of presenting information. Findings. The study revealed the impact of quarantine restrictions due to COVID-19 on the financial and economic activities of business structures and studied trends in the industry. A financial and economic analysis of the activity of enterprises, leaders of the international market in the chosen field of research is carried out. The data in the forecasts for the following periods have been adjusted to take into account the following factors: recognition of assets in the form of rights of use, separation of lease obligations, transfer of lease costs from operating expenses and depreciation assets in the form of rights of use. This made it possible to study the further development of new tools and their impact on future financial and economic performance of enterprises in quarantine conditions. Originality. The analysis, estimation and forecast concerning financial and economic activity of business structures are given and the tendencies of development in the period of quarantine restrictions of COVID-19 are revealed. This analysis makes it possible to make a forecast for the following periods adjusted taking into account quarantine restrictions. Practical value. The results of the study presented in this work can be used by economists, scientists and practitioners to develop and launch investment projects for enterprise development programs.

Анотація. Обґрунтовано, що фактором економічного зростання, підвищення економічної та енергетичної безпеки, збереження навколишнього середовища від згубного впливу наслідків споживання вуглеводневих джерел енергоресурсів є сталий розвиток відновлюваної енергетики. Розглянуто стан і перспективи використання відновлюваних джерел енергії (ВДЕ) у світі. Представлено рейтинг країн за питомою вагою електроенергії, виробленої з ВДЕ у відсотках до первинних джерел за період 2015—2019 рр., який показує, що найбільшу ефективність ВДЕ мають такі країни, як Ісландія, Кенія і Латвія, а найбільше зростання спостерігається в Україні, Великобританії, Туреччині, Данії, Японії, Франції, США і Німеччині. Узагальнено фактори зростання попиту на ВДЕ, зокрема: паритет ціни і продуктивності внаслідок зниження ціни на ВДЕ; підвищення ефективності виробництва енергії внаслідок технологічного прогресу та впровадження інноваційних технологій у ВДЕ; інтеграція енергомереж і збалансування навантаження на них; стимулювання попиту на ВДЕ великими містами — реалізація стратегії «розумного міста», яка включає «розумну» енергетику; розвиток громадського володіння мережами і ВДЕ; активна участь країн, що розвиваються, у поширенні відновлюваної енергетики; зростаюча участь корпоративного сектору в розвитку відновлюваної енергетики. Визначено взаємозв’язок цілей розвитку сфери енергетики щодо її доступності, надійності, стійкості та цілей у галузі сталого розвитку. Так, скорочення масштабів бідності (ціль 1) передбачає розширення доступу до базових ресурсів і послуг, наявності сучасної інфраструктури, елементом якої є ВДЕ; використання екологічно чистої відновлюваної енергетики сприятиме зниженню ризиків для здоров’я (запобігання хворобам і боротьбі з пандеміями) — ціль 3; створення стійкої інфраструктури, сприяння інноваціям (ціль 9) передбачає застосування чистих та екологічно безпечних технологій і сталого розвитку енергетики; використання ВДЕ має синергетичний зв’язок із реалізацією цілі 13 — термінові заходи боротьби зі зміною клімату і його наслідками. Ключові слова: цілі сталого розвитку, зростання економіки, енергетична безпека, відновлювані джерела енергії, вуглеводневе паливо, декарбонізація. Формул: 0; рис.: 0; табл.: 2; бібл.: 17.

The purpose of the article is developing a risk management system in the aviation industry. After analyzing the works of many scientists, such concepts as «risk», «risk management» were considered and their importance in business was highlighted. This article provides a coefficient analysis of the financial condition of one of the largest airlines in Ukraine PJSC «International Airlines of Ukraine». The authors pay special attention to external and internal factors, which are the main result of losses from the decline in air traffic, to regional factors that shape the demand for air traffic within a particular area and directly affect the efficiency of the airline. Therefore, the authors present regional factors that affect the results of economic activity and financial stability of the airline. As a result of the study, we observe that one of the preventive methods of risk identification is targeted management, which in essence is a way to achieve effective business structure in the future. The development of a risk management system should be an integral part of its targeted management. The authors have developed a risk management system for this company, which has a clear structured approach that combines strategy, business processes, staff, technology, experience and knowledge. This system is the basis of the corporate governance system, which requires a long transition period, as well as a significant increase in the professional level of staff. At the risk assessment stage, the authors propose to consider sources of information to compile a risk map. In addition, the authors believe that it is necessary to carry out general monitoring of processes occurring in various departments of the airline in order to identify new, unspecified risks, as well as new business processes that may involve risks. A new risk management process is proposed for this control. Creating an effective risk management system allows to ensure a high level of quality and rationality of management decisions, which enables the company to achieve strategic and tactical goals., Мета статті — розроблення системи ризик-менеджменту на підприємствах авіаційної галузі. Проаналізувавши наукові праці багатьох учених, було розглянуто такі поняття, як «ризик», «управління ризиком», і виділено їхню важливість у підприємницькій діяльності. Проведено коефіцієнтний аналіз фінансового стану однієї з найбільших авіакомпаній України — ПрАТ «Авіакомпанія “Міжнародні Авіалінії України”». Особливу увагу приділено зовнішнім і внутрішнім факторам, які є головним результатом отриманих збитків від зниження авіаперевезень, але неабиякий аспект приділено регіональним факторам, що формують попит на авіаперевезення всередині конкретної території і впливають безпосередньо на ефективність роботи авіакомпанії. Тому подано регіональні фактори, які впливають на результати господарської діяльності та фінансову стійкість функціонування авіакомпанії. У результаті дослідження спостерігаємо, що одним із попереджувальних методів виявлення ризиків є цільове управління, яке за своєю сутністю є шляхом до досягнення ефективної діяльності бізнес-структури в майбутньому. Розроблення системи ризик-менеджменту повинна бути невід’ємною частиною її цільового управління. Розроблено систему ризик-менеджменту для цієї компанії, що має чіткий структурований підхід, який об’єднує стратегію, бізнес-процеси, персонал, технології, досвід і знання. Система є основою системи корпоративного управління, що вимагає тривалого перехідного періоду, а також істотного зростання професійного рівня персоналу. На етапі оцінки ризиків запропоновано враховувати джерела інформації для складання карти ризиків. Крім того, вважаємо, що потрібно здійснювати загальний моніторинг процесів, що відбуваються в різних підрозділах авіакомпанії, з метою виявлення нових, неуточнених раніше ризиків, а також нових бізнес-процесів, які можуть містити ризики. Для цього контролю запропонований новий процес управління ризиками. Створення ефективної системи ризик-менеджменту дозволяє забезпечити високий рівень якості та раціональності ухвалення управлінських рішень, що дає можливість підприємству досягти стратегічних і тактичних цілей.

Мета дослідження. Мета статті полягає в обґрунтуванні заходів аграрної політики країн Європи і держав-членів в умовах пандемії з метою адаптації позитивного досвіду та його використання для удосконалення державної аграрної політики України в контексті використання земель в сучасних умовах. Методологія. У статі використано системний аналіз, таблично-графічний – при дослідженні обсягів світового виробництва зернових культур у натуральному виразі методи аналізу і синтезу, декомпозиції, індукції і дедукції а також комплексний метод, які дозволили сформувати подані у роботі висновки. Результати. Було обґрунтовано сім категорій заходів державного регулювання щодо стримування впливу пандемії COVID-19 та обмежень в ланцюжках поставок агропродовольчих товарів: 1) загальносекторальні та інституційні заходи; 2) інформаційні та координаційні заходи; 3) заходи з торгівлі та товарних потоків (розширення торгівлі або обмеження торгівлі); 4) трудові заходи (заходи біобезпеки та трудові ресурси); 5) сільське господарство та продовольча підтримка (або підтримка сільськогосподарських і продовольчих компаній); 6) загальна підтримка (включаючи пакети, що належать сфері діяльності); 7) продовольча допомога і підтримка споживачів (заходи щодо попиту). Практичне значення дослідження полягає в тому, що основні висновки та пропозиції автора можуть бути використані державними органами для формування ефективної державної аграрної політики України в контексті використання земель.

Мета дослідження. Мета полягає в удосконаленні методичних положень щодо формування конкурентної стратегії сільськогосподарського підприємства в умовах невизначеності зовнішнього середовища та загострення конкуренції в умовах погіршення якості земель. Методологія. У статі використано системний підхід до вивчення економічних явищ і виокремлення основних складових щодо базових маркетингових стратегій; метод групування та порівняння; фінансовий аналіз – для дослідження стану та динаміки фінансових показників підприємства; метод аналізу SWOT – для вибору напрямів і варіантів розвитку ринкових можливостей підприємства. Результати. Було сформовано конкурентну стратегію для ПСП «ДІАР» (с. Завадівка Володарського району Київської області), основним видом діяльності якого за КВЕД є: 01.11 Вирощування зернових культур (крім рису), бобових культур і насіння олійних культур. Процес формування маркетингової конкурентної стратегії ПСП умовно поділений на чотири етапи. Перший етап – це формулювання цілей підприємства. На другому етапі проводяться дослідження зовнішнього та внутрішнього середовища підприємства; здійснюється оцінка факторів, визначених на основі SWOT-аналізу та виконують розрахунок оцінки взаємопов’язаних пар. На третьому етапі обирають стратегію щодо факторів впливу і роблять обґрунтування вибору оптимальної конкурентної стратегії. Четвертий етап – планування реалізації стратегії, що передбачає розробку переліку конкретних заходів для досягнення визначених цілей на довгострокову та середньострокову перспективу. Вибір оптимальної стратегії для ПСП «ДІАР» здійснено з використанням матриці стратегічних альтернатив І.Ансоффа. Практичне значення дослідження полягає в тому, що основні висновки та пропозиції автора можуть бути використані ПСП «ДІАР» для формування та реалізації конкурентної стратегії з метою підвищення ефективності виробництва та якості земель.

Виокремлено підходи до розуміння розвитку в умовах цифровізації, що дозволило сформувати за характерними ознаками три підходи до розуміння поняття «розвиток соціально-економічної системи в умовах цифровізації» - ресурсний, потоковий (процесний), структурний. За кожним з цих підходів шляхом їх систематизації виділено відповідну основу розвитку соціально-економічної системи в умовах цифровізації, причини та наслідки цього процесу, що дозволяє усунути притаманні їм недоліки. Обґрунтовано сутність та зміст цифровізації як економічної категорії. Сутність цифровізації полягає у впровадженні цифрових технологій до кожного елементу ланцюжка створення валової доданої вартості, в процесі впровадження яких виникають нові вимоги до комунікацій, інформаційних систем і сервісів а генерування даних завдяки функціонуванню електронно-цифрових пристроїв, засобів та систем перетворює їх на ключовий фактор сучасного виробництва. Зміст цифровізації розкривається через інформаційно-комунікаційне середовище функціонування соціально-економічної системи, в якому відбувається еволюція економічних, соціальних, виробничих, техніко-технологічних, організаційних, управлінських, та інших відносин всередині суспільства, зміна їх суб'єктивно-об'єктивної орієнтованості, яка викликана розвитком цифрових технологій. Визначено принципи розвитку соціально-економічної системи в умовах цифровізації на основі взаємного врахування існуючих в сучасній економічній теорії загальних та системних принципів розвитку та доповнення їх принципами, що притаманні розвитку в умовах цифровізації економіки, а саме принципами інформаційності, синхронності, мережевості та автоматизації. Запропоновано на основі проведеного парадигмального аналізу наукових досліджень у сфері розвитку аграрного сектору парадигму розвитку аграрного сектору в умовах цифровізації, що діалектично поєднує риси традиційної, мультифункціональної, реконверсійної та технологічної парадигм та на основі їх комбінування дає можливість усунути притаманні цим парадигмам розвитку недоліки. На засадах такої парадигми пошук оптимальних шляхів розвитку відбувається на основі врахування зміни їх характеристик, що викликані впливом факторів різної природи і сили та специфіки сучасних процесів цифровізації. Удосконалено методологію дослідження розвитку аграрного сектору в умовах цифровізації, застосування якої дає змогу досліджувати розвиток аграрного сектору в умовах цифровізації на теоретичному, емпіричному з розподілом його на діагностично-аналітичний й аксіологічний рівнях, з відповідним кожному рівню самостійним інструментарієм, використання якого дає можливість надати глибоку і всебічну характеристику розвитку аграрного сектору в умовах цифровізації. Деталізація методології дослідження розвитку аграрного сектору на теоретичному рівні, що здійснюється на основі методу систематизації існуючого спектру теорій економічних процесів, передбачає при проведенні дослідження відбір як базових так і додаткових теорій, що дозволяє врахувати особливості формування понятійно-категоріального апарату дослідження та способи вирішення актуальних проблем розвитку аграрного сектору в умовах цифровізації. Сформовано концепцію розвитку аграрного сектору в умовах цифровізації що складається з гноселогогічного, методичного, інструментального та практично-аналітичного компонентів, кожен з яких шляхом деталізації розкладено на певні елементи, що забезпечує комплексне стратегічне бачення та визначення сутності, спрямованості, змісту, характеру розвитку аграрного сектору.

The inducible ability of adaptive response by low doses of gamma rays or bleomycin was studied in peripheral blood lymphocytes of healthy donors and in ataxia telangiectasia patients. An adaptive response was found in the lymphocytes of healthy donors pretreated with either gamma rays or bleomycin, however in individuals heterozygous for ataxia only bleomycin was effective. In the two ataxia telangiectasia homozygotes tested no adaptive response was found either after low-dose gamma rays or after bleomycin. The preliminary results indicate that the adaptive response might be infuenced by various factors.

Acellular assay of calf thymus DNA+/-rat liver microsomal S9 fraction coupled with (32)P-postlabelling was used to study the genotoxic potential of organic compounds bound onto PM10 particles collected in three European cities-Prague (CZ), Kosice (SK) and Sofia (BG) during summer and winter periods. B[a]P alone induced DNA adduct levels ranging from 4.8 to 768 adducts/10(8) nucleotides in the concentration dependent manner. However, a mixture of 8 c-PAHs with equimolar doses of B[a]P induced 3.7-757 adducts/10(8) nucleotides, thus suggesting the inhibition of DNA adduct forming activity by interaction among various PAHs. Comparison of DNA adduct levels induced by various EOMs indicates higher variability among seasons than among localities. DNA adduct levels for Prague collection site varied from 19 to 166 adducts/10(8) nucleotides, for Kosice from 22 to 85 and for Sofia from 6 to 144 adducts/10(8) nucleotides. Bioactivation with S9 microsomal fraction caused 2- to 7-fold increase in DNA adduct levels compared to -S9 samples, suggesting a crucial role of indirectly acting genotoxic EOM components, such as PAHs. We have demonstrated for the first time a significant positive correlation between B[a]P content in EOMs and total DNA adduct levels detected in the EOM treated samples (R=0.83; p=0.04). These results suggest that B[a]P content in EOM is an important factor for the total genotoxic potential of EOM and/or B[a]P is a good indicator of the presence of other genotoxic compounds causing DNA adducts. Even stronger correlation between the content of genotoxic compounds in EOMs and total DNA adduct levels detected (R=0.94; p=0.005) was found when eight c-PAHs were taken into the consideration. Our findings support a hypothesis that a relatively limited number of EOM components is responsible for a major part of its genotoxicity detectable as DNA adducts by (32)P-postlabelling.

Principal aims of this study were at first, to find a relevant human derived cell line to investigate the genotoxic potential of PAH-containing complex mixtures and second, to use this cell system for the analysis of DNA adduct forming activity of organic compounds bound onto PM10 particles. Particles were collected by high volume air samplers during summer and winter periods in three European cities (Prague, Kosice, and Sofia), representing different levels of air pollution. The genotoxic potential of extractable organic matter (EOM) was compared with the genotoxic potential of individual carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) as well as their artificial mixtures. Metabolically competent human hepatoma HepG2 cells, confluent cultures of human diploid lung fibroblasts (HEL), and the human monocytic leukemia cell line THP-1 were used as models. DNA adducts were analyzed by (32)P-postlabeling. The total DNA adduct levels induced in HepG2 cells after exposure to EOMs were higher than in HEL cells treated under the same conditions (15-190 versus 2-15adducts/10(8) nucleotides, in HepG2 and HEL cells, respectively). THP-1 cells exhibited the lowest DNA adduct forming activity induced by EOMs (1.5-3.7adducts/10(8) nucleotides). A direct correlation between total DNA adduct levels and c-PAH content in EOM was found for all EOMs in HepG2 cells incubated with 50microg EOM/ml (R=0.88; p=0.0192). This correlation was even slightly stronger when B[a]P content in EOMs and B[a]P-like adduct spots were analyzed (R=0.90; p=0.016). As THP-1 cells possess a limited metabolic capacity for most c-PAHs to form DNA reactive intermediates and are also more susceptible to toxic effects of PAHs and various EOM components, this cell line seemed to be an inappropriate system for genotoxicity studies of PAH-containing complex mixtures. The seasonal variability of genotoxic potential of extracts was stronger than variability among the three localities studied. In HepG2 cells, the highest DNA adduct levels were induced by EOM collected in Prague in the winter period, followed by Sofia and Kosice. However, in the summer sampling period, the order was quite opposite: KosiceSofiaPrague. When the EOM content per m(3) of air was taken into consideration in order to compare real exposures of humans to genotoxic compounds in all three localities, extracts from respirable dust particles collected in Sofia exhibited the highest genotoxicity regardless of the sampling period. The results indicate that most of DNA adducts detected in cells incubated with EOMs have their origin in low concentrations of c-PAHs representing 0.03-0.17% of EOM total mass. Finally, our results suggest that HepG2 cells have a metabolic capacity for PAHs similar to human hepatocytes and represent therefore the best in vitro model for investigating the genotoxic potential of complex mixtures containing PAHs among the three cell lines tested in this study.

NAT2 as phase II enzyme is involved in the detoxification/activation of various drugs, environmental substances and carcinogenic compounds. A genotyping approach has been used to investigate NAT2 genotype with putative relevance in lung cancer in population of 110 Slovak-Caucasians patients and 167 non-malignant individuals from the same region. Slow acetylation was not observed to be a significant risk factor of lung cancer development (OR=1.19; 95% CI: 0.71-1.99). However, one genotype responsible for slow acetylation (NAT2*5B/*6) was observed significantly more frequently in lung cancer patients with squamous cell carcinoma compared with control subjects (OR=2.24; 95% CI: 1.14-4.34). Stratified analysis showed an increasing impact of the specific allelic combination NAT2*5B/*6 in non-smokers (OR=6.5; 95% CI: 1.25-15.08). In the case of squamous lung carcinoma an analysis revealed a tendency to adversely affect cancer risk in the individuals with the mentioned genotype in younger than 60 years (OR=3.14; 95% CI: 0.98-9.72) non-smokers (OR=10.40; 95% CI: 1.35-118.89) and in females (OR=4.25; 1.08-16.25). Additional studies are needed to confirm the results we observed and to assess the impact of other effects (specific allelic combinations, sex differences and histological subtype of lung cancer) on NAT2 susceptibility in lung carcinogenesis.

Renin-angiotensin system (RAS) have been extensively studied in last few decades. RAS regulates blood pressure, water and electrolytes balance. The disorders in function of RAS may play a potential role in development of some complex diseases like: hypertension, myocardial infarction, stroke, nephropathies and renal failure, chronic obstruction pulmonary disease and many more. RAS may take part in formation and progression of these diseases. In this work we focus on molecular biology of RAS and polymorphisms of RAS genes.

Many genes involved in the metabolism of carcinogens have been found to be polymorphic in the human population, and specific alleles are associated with increased risk of cancer at various sites. The etiology of most commonly occurring cancers cannot be explained by allelic variability at a single locus. A combined analysis of two polymorphic enzymes, glutathione S-transferase M1 (GSTM1), microsomal epoxide hydrolase (EPHX1)) and their implication as lung cancer risk factors was performed in a case- control study of non small cell lung cancer. Polymerase chain reaction (PCR) or PCR-RFLP-based methods were used to detect variant genotypes of GSTM1 and EPHX1 (113Tyr-113His in exon 3 and 139His-139Arg in exon 4) in 150 controls and group of lung cancer patients (n=121). The slow 113His EPHX1 allele tended to be more frequent among the patients (frequency 0.587) than among the controls (0.320) (Fisher s exact test, p=0.33). The combined EPHX1 homozygote genotype His113/His139 (predicted very slow activity) versus all other genotype combination was associated with an increased risk of lung cancer (OR=2.29; 95% C.I.=0.94- 5.82), particularly in non-smokers (OR=11.23; 95% C.I.=1.48- 88.41). Polymorphism in GSTM1 had no statistically significant impact on lung cancer risk alone (OR=1.09; 95% C.I.: 0.65-1.82). However, obtained the results revealed that combinations GSTM1 null with homozygote His113/His139 genotype (predicted very slow activity EPHX1) significantly increased lung cancer risk (OR=3.65; 95% C.I.: 1.04-16.07). No overall relationship between genotype combinations predicted high EPHX1 activity and lung cancer risk was confirmed in all followed respects. However, the number of investigated individuals in our study was relatively small, therefore these findings should be judged with circumspectness.

The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors.

We tested the codon 72 single nucleotide polymorphism (SNP) of the tumor suppressor gene p53 for association with lung cancer. In our hospital-based case-control study, 168 lung cancer patients (134 males and 34 females) and 148 controls without malignant diseases were recruited. The genotype characteristics were determined by PCR-based RFLP method using DNA extracted from peripheral blood. Only in lung cancer patients but not in the controls we found both significant decrease of A1 allele of the p53 codon 72 (p=0.024, OR 0.56, 95% CI 0.43-0.72) and A1/A1 homozygous genotype (p=0.006, OR 0.27,95% CI 0.15-0.51). The results of this study suggest a protective effect of A1 allele against lung cancer.

Two p53 germline polymorphisms, a BstUI in exon 4 and a MspI in intron 6 were studied using polymerase chain reaction (PCR) based methods in 50 patients with bladder cancer and 145 healthy controls. Increased frequencies of the BstUI and MspI A2 alleles were found to be associated with statistically non-significant (p = 0.2308 and p = 0.5959) but increased odd ratios for bladder cancer (OR 1.44, 95% CI 0.82-2.27 and OR 1.20, 95% CI 0.61-2.33). Statistically significant difference between patients with bladder cancer and controls was found in the distribution of MspI genotypes. There was a significantly lower proportion of the heterozygous A1A2 genotype in all patients but not in controls (p = 0.0354). The results of this study suggest that BstUI and Msp1 germ line polymorphisms of the tumor suppressor gene p53 marginally modify the risk of bladder cancer.

Several genes involved in the metabolism of carcinogens have been found to be polymorphic in the human population, and specific alleles are associated with increased risk of cancer at various sites. This study is focused on the polymorphic enzymes glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) that are involved in the detoxification of many xenobiotics involved in the etiology of bladder cancer. To investigate the role of GSTM1 and GSTT1 in bladder carcinogenesis, the polymerase chain reaction was used to determine GSTM1 and GSTT1 genotypes of cancer patients (n = 76) and controls (n = 248). The proportion of putative risk GSTM1 null genotype in the case group was 52.6%, compared to 49.6% in the control group, but the GSTT1 0/0 frequency in the bladder cancer group was significantly higher (P = 0.04) in comparison with the control group (27.6 vs 16.9%). Individuals lacking the GSTT1 gene are at an approximately 1.9-fold higher risk (OR = 1.87, C.I. 95% = 1.03-3.42) of developing bladder cancer in comparison with individuals with at least one active allele in the GSTT1 locus. A significantly higher incidence of GSTM1 deletion genotype (P = 0.02) was found in smokers with bladder cancer compared to the controls (70.6 vs 49.6%). Smokers lacking the GSTM1 gene are at an approximately 2.4-fold higher risk of bladder cancer (OR = 2.44, C.I. 95% = 1.10-5.30). The effect of smoking associated with the GSTT1 0/0 genotype was not found to affect the risk of bladder cancer.

Apoptosis or programmed cell death is a physiological process which occurs at different biological states as well as at disease process. Morphologically it is characterized by the chromatine condensation and other changes with preserved integrity of plasmatic membrane. The major and most frequently studied biochemical characteristic of apoptosis is a DNA fragmentation. In our paper attention is directed to the early biochemical changes in cell membranes, i.g., the externalization of phosphatidylserine, hydrolysis of sphingomyeline on the ceramide and activation of phospholipases especially phospholipase A2. In one part we described the changes of cysteine proteases (caspases), which play a key role in the execution of apoptosis. These biochemical changes are associated with ceramide signalization of apoptosis. Briefly are presented also some dates about apoptosis induction with reactive oxygen radicals and the role of the arachidonic acid metabolites in this process. We consider the investigation and determination of these changes as important parameters of apoptosis at some diseases, e.g., cancer or degenerative diseases, and of their treatment.

Paper provides a survey of the basic knowledge on the genetic polymorphism of enzymes involved in the metabolism of medicinal drugs and other xenobiotics. The major implications of this phenomenon have been described, namely the interindividual variability in the therapeutic effect of drugs differently metabolised by the polymorphically determined enzymes, or the interindividual variability in the susceptibility to neoplastic processes related to the polymorphically determined enzymes metabolising xenobiotics. Recent advances in the understanding of the molecular genetics of enzymes metabolising drugs and other xenobiotics (particularly cytochrome P-450, glutathione S-transferase, N-acetyltransferase, UDP-glucoronosyltransferases and others), help to understand the molecular basis of several genetic polymorphisms. Present article reviews the current status of studies on polymorphism of xenobiotics-metabolising enzymes and brings a discussion to their pharmacotherapeutical relevance and to their significance for identification of susceptible individuals/subgroups in the carcinogen exposed population.

The adaptive response and reciprocal adaptive response induced in vitro by exposure to low doses of gamma rays (0.05 Gy) or bleomycin (0.05 microg/ml) in human peripheral blood lymphocytes were assessed by the frequency of chromosome aberrations. Gamma rays (1.5 Gy) or bleomycin (1.5 microg/ml) were used as the challenge doses. In the experiments, blood samples from 5 healthy donors were investigated. It has been found that low doses of bleomycin and gamma rays induced a reciprocal adaptive response to high doses of gamma rays or bleomycin. Moreover, the results confirmed that the adaptive response did not correlate with the radiosensitivity of the peripheral blood lymphocytes.

A combined analysis of two polymorphic enzymes, glutathione S-transferase mu (GST M1) and q (GST T1) and their implication as cancer risk factors was performed in a case-control study of lung and bladder cancers. Using a multiplex polymerase chain reaction (PCR) based method, the frequency of the homozygous deleted GSTM1 and GSTT1 genotypes was examined in 117 lung cancer patients, 67 urinary bladder cancer patients, and in a community-based sample of 248 healthy, unrelated individuals. In both cancer groups the frequency of the GSTM1 null genotype was higher in comparison with that of the control group (59% and 59.7% vs. 49.6%), but this increase did not reach statistical significance (p0.05). After grouping by the smoking status, among smokers in both cancer groups (62.1% in lung cancer and 71.4% in the bladder cancer group, respectively) there were statistically significantly (p0.05) increased frequencies of the GSTM1 deletion genotype as compared to the control group (49.6%). Smokers with absence of the GSTM1 gene were at an approximately 1.7-fold higher risk for lung cancer (odds ratio--OR = 1.67, 95% confidence interval--CI 95% = 1.0-2.7, p = 0.04) and an approximately 2.5-fold higher risk for bladder cancer (OR = 2.54, CI 95% = 1.2-5.5, p = 0.02). As related to GSTT1, our study demonstrated an overall GSTT1 effect on bladder cancer risk. Individuals with absence of the GSTT1 gene were at an approximately 2.5-fold higher risk of developing bladder cancer. In the lung cancer cases, the frequency of the putatively high risk GSTT1 null genotype was not increased as compared with controls. No effect of smoking was found on risk of lung and bladder cancer associated with the GSTT1 0/0 genotype. In combined analysis, the obtained results suggested that individuals who were both GSTM1 null and GSTT1 null may be at increased risk because they lack both enzymes. The findings suggest that the GSTM1 null genotype may be associated with susceptibility to lung and urinary bladder cancer in dependence on the exposure to carcinogens in cigarette smoke and that the GSTT1 null genotype is not a critical factor in mediating the risk of lung cancer, but may be associated with an increased susceptibility to bladder cancer.

Pharmaceutic tar used in the treatment of psoriasis has a high contents of polycyclic aromatic carbohydrates which are considered to be carcinogenic.The study is aimed at the estimation of the genotoxic risk arising from the treatment of psoriatic patients by pharmaceutic tar. The estimation is performed by biomonitoring.The used methods included: bacterial test on TA 98 strain of Salmonella typhimurium aimed at the assessment of mutagenity of urine and cytogenetic test aimed at the assessment of chromosomal aberrations in peripheral lymphocytes.The exposition of psoriatic patients to pharmaceutic tar significantly increased the index of mutagenity as an index of the presence of mutagen in urine, as well as the occurrence of chromosomal aberrations in peripheral lymphocytes.The results of monitoring have indicated that psoriatic patients treated by pharmaceutic tar are endangered by an increased genotoxic risk. (Tab. 2, Ref. 17.)

To assess the genetic control of the induction of the adaptive response after low-dose ionizing radiation, the frequencies of chromosome aberrations were evaluated in four pairs of monozygotic twins, two pairs of dizygotic twins, and in nine unrelated individuals. Stimulated cells were exposed to adaptive dose of 5 cGy gamma rays at 24 h and challenge dose of 150 cGy gamma rays at 42 h. Cells were fixed at 48 h and chromatid and isochromatid breaks were evaluated. The adaptive response was found in two pairs of monozygotic twins, but not in the two other pairs. Individual differences in adaptive response between the members of monozygotic twins were very small. In contrast, the variability in the adaptive response between the members of dizygotic twins was much greater and was similar to that observed in the unrelated donors. The results confirmed that heterogeneity in the adaptive response after exposure to low-dose gamma rays was controlled genetically to a considerable extent.

Virtually any eukaryotic cell can be processed for analysis of DNA damage using the comet assay. The most commonly examined human cells are lymphocyte populations. However, many parameters can affect the response of lymphocytes to the assay in terms of the ability to detect damage. The response of cultivated lymphocytes in the comet assay indicated cycle-dependent differences. The cell cycle position has been shown to affect the results obtained using both the alkaline and neutral assays. This is primarily a reflection of the complications of including S-phase DNA. In the alkaline assay, replicating structures are interpreted as strand breaks when denatured, increasing the level of detectable damage. We performed the alkaline comet assay to detect differences in the extent of DNA in stimulated human lymphocytes collected at different sample times after mitogen stimulation. Our results clearly indicate that proliferating lymphocytes have a greater migration of DNA (measured with the comet assay as DNA damage) than quiescent lymphocytes. The lymphocytes collected at 36, 42, and 48 h after mitogen stimulation showed a significantly increased extent of DNA migration in comparison to the lymphocytes collected at 0 and 24 h after stimulation. It, probably, can be explained by the higher frequency of the S phase cells in lymphocyte populations collected at 36, 42, and 48 h. Sites of active DNA replication during the S phase behave like single-strand breaks when denatured in alkali, and their presence may result in a significant increase of the tail moments in S phase cells.

The comet assay, a relatively new method for DNA strand break detection in individual cells, is becoming a major tool for environmental biomonitoring. One approach for assessing the possible environmental consequences of hazardous waste pollution involves the assessment of genotoxic damage (and other effects) in sentinel organism. The single cell gel electrophoresis (SCGE) technique or comet assay. because of its simplicity, sensitivity, and need for only small numbers of cells, has been suggested as an ideal technique for such studies. An important advantage of the technique is that it is applicable to any eukaryotic organism and cell type. Verschaeve et al. (1993) conducted a pilot study using alkaline comet assay to assess the extent of DNA damage in coelomic leucocytes (coelomocytes) of earthworms (Eisenia foetida) maintained in different soil samples as an indicator of soil pollution. The aim of our study was to evaluate the usefulness of monitoring single strand breaks in coelomocytes for assessing genotoxicity of pollutants in coke oven area. We exposed earthworms to samples of soils obtained from polluted areas of a coke oven. All samples gave a significantly higher comet tail moment that those obtained from worms kept in laboratory conditions (standard black earth = internal controls) and worms kept in soils from control areas (= external controls). Our results show that the comet assay applied to earthworm is very valuable for monitoring and detection of genotoxic compounds in terrestrial ecosystems.

An epidemiological study was performed on 42 workers from coke works with the aim to evaluate the usefulness of monitoring single strand DNA breaks (SSBs) in human lymphocytes to assess exposure to polycyclic aromatic hydrocarbons (PAHs) as well as the usefulness of SSBs induction as an indicator of biological effects of PAHs. SSBs can be readily quantitated by a simple fluorometric assay of DNA unwinding. Compared with the control group, statistically significant increase in SSBs was observed in coke oven workers occupationally exposed to PAHs. These findings are in agreement with previous results obtained by a different method of measuring DNA damage in subjects exposed to high PAH levels. The findings confirmed that SSBs determination in human lymphocytes reflected the exposure to PAHs and the FADU method appears to be useful in the revelation of effects of occupational exposure to industrial air pollutants such as PAHs.

Trisomy 21 is the most frequent chromosomal disorder which is associated with advanced maternal age.The aim of our work was to examine the risk of trisomy 21 occurrence in a group of pregnant women subdued to prenatal cytogenetic examination.The examined group consisted of 1128 pregnant women. The cells for cytogenetic analysis were obtained by means of transabdominal amniocentesis during the second trimester of pregnancy. Cultivation of amniocytes lasted 15-20 days. The chromosomes were stained by a conventional and G-striping method.Cytogenetic analyses have indicated that the aberrant karyotype was present in 32 (2.82%) out of 1128 fetuses. In addition the results have confirmed that trisomy represented the most frequent chromosomal aberration (60%) detected by means of prenatal cytogenetic diagnostic examinations and the risk of its incidence increased exponentially in women who were older than 35 years of age.The prenatal cytogenetic diagnosis represents a significant role in the prevention of hereditary conditioned chromosomal disorders. (Tab. 1, Fig. 1, Ref, 13.)

Examination of patients exposed for prolonged periods to black coal tar used in dermatology for the treatment of psoriasis revealed its carcinogenic effect. The objective of the present work was to assess the mutagenicity of urine samples from psoriatic patients treated with pharmaceutical black coal tar before treatment, and 14 and 28 days after application of the preparation.To a group of 19 patients with psoriasis vulgaris (12 men, mean age 43.3 +/- 3.96 years and 7 women, mean age 44.7 +/- 4.02 years) daily black coal tar in the form of Sack's tincture for a period of 28 days was applied to 10 - 80% of the body surface, i.e. 1000 - 13,000 cm2 of skin, amounting to 10 - 40 g. The mutagenic activity of urinary extracts was assessed by means of the Ames test on bacterial strain TA 98. It was revealed that urine samples from all patients exposed during the therapeutic procedure has a greater mutagenic activity, as compared with controls, whereby the mutagenicity index was higher in smokers (2.1) than in non-smoker patients (1.88) in the presence of the metabolic activating system. The elevated values of the mutagenicity index were recorder after the 14th day (2.25) and after the 28th day of treatment (2.07), as compared with controls (0.93); p0.05. Before the onset of treatment the mutagenicity index was 1.64.The assembled results confirm the view of an increased genotoxic risk in psoriatic patients treated with preparations containing black coal tar.

The ability to induce an adaptive response by low doses of gamma rays was studied in normal and trisomic lymphocytes (47, XX or XY, +21). The results indicate the presence of an adaptive response in lymphocytes of 3 normal donors, but in lymphocytes of 5 donors with trisomy 21 no significant adaptive response after irradiation with a low dose of gamma rays was found. There was similar chromosomal radiosensitivity in normal and trisomic lymphocytes (47, XX or XY, +21) irradiated with 1.50 Gy at the 48th hour after stimulation.

The paper deals with the genetic risk of advanced age of women assessed on the basis of prenatal cytogenetic analysis during the second trimester of gestation. The examined group comprised 614 pregnant women older than 35 years. The cells for chromosomal analysis were obtained by transabdominal amniocentesis during the 16th to 18th week of gestation. Cytogenetic examination revealed that the general risk of an aneuploid foetus in women of more advanced age is 2.12% and the most frequently encountered chromosomal aberration was trisomy 21 which was confirmed in 1.30 cytogenetically examined foetuses.

An 86 MW bottoming cycle has been designed based on the Kalina cycle principles previously reported by the authors. It is designated as Kalina Cycle System 6 (KCS6). It uses an ABB Type 13E gas turbine topping cycle to produce a 227 MW combined cycle having a heat rate (LHV) of 6460 Btu/kWh (52.8%). The working fluid is a 75% aqua ammonia mixture. Equipment and installation costs were developed for KCS6 and a baseline two-pressure steam bottoming cycle. The KCS6 turbine was designed with input from ABB. Compared to the two-pressure steam bottoming cycle, KCS6 provides an additional 12.1 MW (16.4%). The estimated cost of the bottoming cycle is $1,058/kW vs. $1,033/kW for the steam plant. The KCS6 heat acquisition equipment (boiler and recooler) and distillation/condensation subsystem represent the two major additions to cost over the steam plant. On the other hand, the turbine is less expensive, mostly due to the elimination of the large condensing stages. An economic analysis of the KCS6 plant is presented using the value of the additional output as the decision-making economic variable. The analysis is based on a model which considers capital cost, heat rate and near-term world-wide fuel prices. At $4.25/106 Btu fuel, the KCS6 costs approximately $7 million less than the value of its output.

Experimental results confirmed that the best period of cultivation of human peripheral lymphocytes for chromosomal analyses in subjects exposed to mutagens and carcinogens is 44-48 hours when the dividing lymphocytes are in the first cellular cycle. With prolongation of the cultivation period of lymphocytes the values of chromosomal aberrations decline because in subsequent cellular cycles their number declines as a result of mitotic deaths of cells which contain unstable types of aberrations.

Information on the new branch of medical genetics--genotoxicology--is presented. The results obtained so far in the field of genotoxicologic research are briefly reviewed and the contribution of our departments is outlined. The conclusion indicates further trends in basic and applied research and emphasizes the necessity to take advantage of the knowledge and information achieved in genotoxicologic research in social practice.

The frequency of chromosomal aberrations was studied in myelokaryocytes of mice and rats continuously irradiated for 90 days at a dose rate of 50R/day. The curves expressing the frequency of chromosomal aberrations in continuously irradiated mice and rats are biphasic. The first phase is similar for the two species and is characterized by an increase in the frequency of cells with chromosomal aberrations. In the second phase, the frequency of cells with chromosomal aberrations had stabilized at a level of 25--28% in rats, and in mice the values of aberrant cells were gradually increasing until the end of irradiation when they reached 40.1%. In contrast to it, the distribution of aberrations of the chromatid and chromosomal types did not change throughout the experiment in both animal species.