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Made available in DSpace on 2018-12-11T17:16:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Bauhinia holophylla (Bong.) Steud. (Fabaceae) is a plant used in Brazilian folk medicine to treat diabetes and inflammation. This study evaluated the phytochemical properties, cytotoxic, apoptotic, mutagenic/antimutagenic effects and alterations in gene expression (RNAm) in HepG2 cells treated with the B. holophylla extract. The phytochemical profile highlight the presence of flavonoids isorhamentin and quercetin derivates. The MTT assay was used to evaluate the cytotoxicity of different concentrations for different treatment times. Three concentrations (7.5, 15, 30 µg/mL) were chosen for assessment of apoptosis (AO/EB), mutagenicity (micronucleus), and cell cycle kinetics (flow cytometry). Thereafter, the concentration of 7.5 µg/mL was chosen to evaluate the protective effects against DNA damage induced by benzo[a]pyrene (B[a]P). At concentrations higher than 7.5 µg/mL (between 10 and 50 µg/mL), the extract was cytotoxic, induced apoptosis, and caused antiproliferative effects. However, it did not induce micronucleus and a reduction of apoptotic and micronucleated cells was observed in treatments that included the extract and B[a]P. The protective effect is attributable to the presence of flavonoids, described as antioxidants, inhibitors of DNA adduct and activators of detoxifying enzymes. The results of the present study such as absence of cytotoxic and mutagenic effects and protective effects against known carcinogens suggest that B. holophylla has potential for use soon as herbal medicine. Department of General Biology Biological Sciences Center State University of Londrina - UEL, Rod Celso Garcia Cid PR 445, Km 380, University Campus, P.O. Box 6001 Department of Biological Sciences Faculty of Pharmaceutical Sciences of Araraquara São Paulo State University - UNESP Campus Litoral Paulista São Paulo State University - UNESP Department of Biological Sciences Faculty of Sciences of Bauru São Paulo State University – UNESP Department of Botany Biosciences Institute São Paulo State University - UNESP Institute of Biological Investigation Clemente Estable Department of Biological Sciences Faculty of Pharmaceutical Sciences of Araraquara São Paulo State University - UNESP Campus Litoral Paulista São Paulo State University - UNESP Department of Biological Sciences Faculty of Sciences of Bauru São Paulo State University – UNESP Department of Botany Biosciences Institute São Paulo State University - UNESP FAPESP: 2009/16147-5 FAPESP: 2009/52237-9 FAPESP: 2012/01996-0

Exposure of human populations to cadmium (Cd) and Lead (Pb) from food and products thereof may produce effects in organssuch as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd and Pb have been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are important for the public health (Fowler, Toxicol Appl Pharmacol 238:294–300, 2009). The ability to evaluate Cadmium and Lead exposure of these elements through monitoring is a step towards understanding their health effects. We have carried out a monitoring program, in 3 years, in different areas of Albania. Our target was the monitoring of the accumulation of Cd and Pb in the kidneys of ovine/caprine. The samples were chosen because their products are commonly used by the population. The determination of these two chemical elements was performed in according with EC No 1881/2006. During the entire monitoring period only two samples have been found to be noncompliant. Both samples resulted to be from south of Albania, (Gjirokastra region).

The objective of this article is to review genotoxicologic and carcinogenic profile of the artificial sweetener aspartame. Aspartame is a synthetic dipeptide, nearly 180–200 times sweeter than sucrose. It is the most widely used artificial sweetener especially in carbonated and powdered soft drinks, beverages, drugs and hygiene products. There is a discussion ongoing for many years whether aspartame posses genotoxic and carcinogenic risk for humans. This question led to many studies to specify the adverse effects of aspartame. Therefore, we aimed to review the oldest to latest works published in major indices to gather information within this article. With respect to published data, genotoxicity and carcinogenicity of aspartame is still confusing. So, consumers should be aware of the potential side effects of aspartame before they consume it.

Recently, numerous experimental reports as well as clinical trials suggested a possible therapeutic role of selective cyclooxygenase-2 (COX-2) inhibitors in the treatment of various tumors. COX-2 is known to convert procarcinogens to carcinogens and is upregulated in several malignant tumors. Its overexpression seems to correlate with aggressive disease and poor survival. In human schwannomas, COX-2 expression was observed in the cytoplasma and perinuclear regions of tumor cells. The available data suggests involvement of COX-2 in the development and growth of human schwannomas by regulating angiogenic factors and inhibition of tumor cell apoptosis by production of prostaglandins, particularly PGE2. Furthermore, diverse neurotrophic factors have been also suggested a biological role in development, maintenance, and growth of schwannomas. Selective COX-2 inhibitors have a potential role for targeted therapy against schwannomas.

Benzo[a]pyrene (BaP) is a highly carcinogenic substance that is created as an unintentional byproduct of combustion processes.

The urinary bladder is a muscular hollow sac that sits on the floor of the pelvis and stores urine. A layer of epithelial cells lines the internal wall of the bladder. Since these cells are constantly exposed to numerous carcinogens prior to disposal through urine; cigarette smoking and occupational exposure to carcinogens increases the risk of developing bladder cancer. Another common human health issue related to the bladder is the sudden involuntary contraction of the bladder muscle that causes overactive bladder. It is an exceedingly common problem affecting men and women of all age groups. Two major discoveries have propelled expectations regarding the use of capsaicin as a potential therapeutic agent for bladder related diseases; (i) that capsaicin functions through the transient vanilloid receptor and (ii) vanilloid receptor has been shown to be present in the urinary tract. While capsaicin has been used to reduce bladder overactivity in people, its use in cancer therapy is still in preclinical stages. In this chapter we examine the pathology and molecular mechanisms of these two bladder diseases, the current treatment strategies and discuss the potential use of capsaicin as a therapeutic agent. In conclusion, we anticipate that development of capsaicin, as an intravesical agent for recurrent bladder cancer, will happen sooner rather than later.

Agent Orange consist of 50% n-butyl esters of 2,4,5-trichlorophenoxy acetic acid and 50% 2,4-dichlorophenoxyacetic acid. These compounds are chemical plant growth regulators, which mimic the effect of plant hormones, provoking plants into frantic growth before they wither and die. The toxicity of Agent Orange is attributed to the contamination with dioxin, which was perhaps the most toxic molecule ever synthesized by man. Agent Orange’s actual effect on human health remained controversial because even though dioxin at certain levels was clearly capable of causing serious diseases, those same diseases could also result from other causes. Dioxin is a persistent organic pollutant that will accumulate in animal fat and plant tissues and therefore can enter the food chain. The US National Toxicology Program has classified dioxin as “known to be a human carcinogen”, causing namely, chronic lymphocytic leukemia, soft tissue sarcoma, non-Hodgkin lymphoma and Hodgkin disease with sufficient evidence of an association. Severe acute intoxication of dioxin caused chloracne, porphyria, transient hepatotoxicity, and neurotoxicity. Chronic persistence of dioxin in the human body may contribute to development of atherosclerosis, hypertension, diabetes, vascular changes, and neuropsychological impairment several decades after massive exposure. However, such chronic effects are nonspecific and multifactorial. This paper elaborates the aforementioned and other health effects of Agent Orange.

At room temperature acetaldehyde (ethanal) is a flammable, colourless gas with a fruity odour. In 2009, the International Agency for Research on Cancer of the world health organisation classified acetaldehyde as a Class 1 toxin (human carcinogen) [2]. Acetaldehyde is an aldehyde that is highly reactive and toxic, causing damage at the cellular and genomic levels. The main source of the exposure of the general public to this toxin is through consumption of alcohol. In vivo, ethanol is predominantly metabolised to acetaldehyde. However, there are many natural and manufactured sources of acetaldehyde and even those who are teetotal are exposed to this carcinogen. The development of cancer is a multifactorial process in which acetaldehyde has an important role. However, exposure to acetaldehyde and therefore risk of the associated cancers is affected by a complex matrix of behavioural, dietary and genetic factors. Despite the widespread prevalence of acetaldehyde, exposure to the toxin can be limited. For example, potential public health measures to reduce acetaldehyde exposure include reduction of smoking and alcohol consumption. For such measures to be effective it is important to concurrently sensitise the general public to the potential adverse effects of acetaldehyde.

In this chapter, the criteria of inclusion of infectious agents in the short and extended lists of biological carcinogens are discussed. We also propose the criteria for the credibility of the connection between the non-viral infectious agent and cancer.

In this chapter, we briefly describe the general mechanisms of biological carcinogenesis. They can be divided into the three groups: metabolic mechanisms, immune mechanisms and mechanisms mediated by the carcinogenic activity of the bacterial and protozoan toxins. For the simplicity, we note only the very basic moments, since, according to our united opinion, only these issues are importaint for the conceptual understanding of the problem.

In this chapter, we denote the list of potentially carcinogenic infectious agents which are not included into the IARC list. In addition, we postulate the principles of the study design in the field of biological carcinogenesis.

Cadmium is known for its toxicity in animals and man as it is not used in these species. Its only role in biology is as a zinc replacement at the catalytic site of a particular class of carbonic anhydrases in some marine diatoms. The toxicity of cadmium continues to be a significant public health concern as cadmium enters the food chain and it is taken up by tobacco smokers. The biochemical basis for its toxicity has been the objective of research for over 50 years. Cadmium damages the kidneys, the lungs upon inhalation, and interferes with bone metabolism. Evidence is accumulating that it affects the cardiovascular system. Cadmium is classified as a human carcinogen. It generates oxidative stress. This chapter discusses the chemistry and biochemistry of cadmium(II) ions, the only important state of cadmium in biology. This background is needed to interpret the countless effects of cadmium in laboratory experiments with cultured cells or with animals with regard to their significance for human health. Evaluation of the risks of cadmium exposure and the risk factors that affect cadmium’s biological effects in tissues is an on-going process. It appears that the more we learn about the biochemistry of cadmium and the more sensitive assays we develop for determining exposure, the lower we need to set the upper limits for exposure to protect those at risk. But proper control of cadmium’s presence and interactions with living species and the environment still needs to be based on improved knowledge about the mechanisms of cadmium toxicity; the gaps in our knowledge in this area are discussed herein.

A common dietary contaminant, aflatoxin B1 (AFB1), has been shown to be a potent mutagen and carcinogen in humans and many animal species. Since the eradication of AFB1 contamination in agricultural products has been rare, the use of natural or synthetic free radical scavengers could be a potential chemopreventive strategy. Boron compounds like borax (BX) and boric acid are the major components of industry and their antioxidant role has recently been reported. In the present report, we evaluated the capability of BX to inhibit the rate of micronucleus (MN) and sister chromatid exchange (SCE) formations induced by AFB1. There were significant increases (P

Of late, flavonoids, a class of polyphenolic compounds ubiquitously present in the human diet have gained increasing attention in cancer prevention. Defining the anti-cancer mechanisms of quercetin, a major dietary flavonoid has been the topic of intense research over the last two decades. Evidences from experimental studies have shown that quercetin not only offers protection against chemically induced cancers but also suppresses the growth of cancer cells in vitro and in vivo by enhancing carcinogen detoxification and antioxidant defences, inducing cell cycle arrest and apoptosis, inhibiting matrix invasion and angiogenesis, and modulating intracellular signalling circuits. Epidemiological studies across different populations have also indicated that quercetin intake is associated with reduced risk of various cancers. This review summarizes the preclinical and clinical data on the anti-cancer effects of quercetin, the key molecular mechanisms of action, its synergistic interactions, and adverse side effects to warrant further clinical evaluation of quercetin for cancer prevention and therapy.

Cyanobacteria (blue-green algae) produce a variety of harmful ­compounds known as cyanotoxins. Microcystin-LR (MC-LR) and nodularin (NOD) are two potent cyanotoxins with strong hepatotoxic activity which pose a major risk to animals and humans, causing illness and death. Several methods for the detection and degradation of these toxins have been developed over the last years due to MC-LR and NOD strong toxic effects. An electrochemical investigation of MC-LR and NOD electrochemical behaviour, as well as their chemical degradation, is described and emerges as an innovation in the cyanotoxins detection field. The MC-LR and the NOD-DNA interactions were investigated using a DNA-electrochemical ­biosensor, adding more data to the studies of genotoxicity and carcinogenic potential associated to these toxins.

The first step in cancer development is the transformation of a primary cell into an immortalized state. Characteristics of a transformed cell include increased proliferation, loss of contact inhibition and attachment, and the ability to form tumors in mice. Electrical cell substrate impedance sensing (ECIS) is the measurement of resistance and reactance across an electrode containing the growing cells. As they grow, the characteristics of transformed cells can be evaluated including migration and invasion. This chapter will review the current uses of ECIS and speculate on its future uses in cancer biology. ECIS has allowed the experimental evaluation of compounds that induce cellular transformation (i.e. potential carcinogens) and individual pathways involved in aspects of cellular transformation. Also explored is the possibility of using ECIS as a high throughput screen of anti-cancer compounds. In the future, ECIS could be used to evaluate “personalized” anti-­cancer treatments where anticancer compounds are tested on an individual’s cancer cells in order to design personalized anti-proliferation or anti-metastasis treatments.

Bladder cancer is a major public health burden. Tumor resection with possible intravesical treatments for superficial disease, and cystectomy or chemotherapy with radiation protocols for invasive bladder cancer have associated limitations and large costs. In addition, exposure to carcinogens contributes to the majority of bladder cancer risk. All of these represent profound opportunities to use nutraceuticals for improvement of current bladder cancer prevention and treatment. We discuss the clinical opportunities for use of nutraceuticals in bladder cancer prevention and treatment, including preventing the first occurrence of bladder cancer in high risk populations, delaying progression of the disease, use in combination with existing intravesical agents, and delaying or preventing radical cystectomy. We review randomized controlled trials of nutraceuticals in bladder cancer, current promising chemopreventive agents under preclinical development for bladder cancer prevention, and future directions of bladder cancer chemoprevention, including the concept of individualized bladder cancer chemoprevention.

Some international studies which were already quoted (Chapter on Foods and Breast Cancer) had shown inconsistent increases in the risk associated with the intake of fats. Besides, the intake of meats – considered as a marker of the fats intake – has been associated with an increased risk of BC. Years ago it was suggested that heterocyclic amines derived from the cooking process of meats played a role as a potential carcinogen through the character of cancer initiator. The identification of a possible independent effect of meat was something of considerable practical importance, indeed.

The in vitro cytotoxic potentials of Furo[3,2-c]pyran-4-one derivatives in human lymphocytes were investigated. Blood samples were obtained from six healthy donors, non-smoking volunteers, which were incubated and exposed to increasing concentrations (0.05, 0.1, 0.5, 1 and 2 mg/mL) of Furo[3,2-c]pyran-4-one derivatives which are methyl 2-methoxy-7-(4-methylbenzoyl)-6-(4-methylphenyl)-4-oxo-4H-furo[3,2-c]pyran-3-carboxylate (1a) and methyl 2-methoxy-7-(4-methoxybenzoyl)-6-(4-methoxyphenyl)-4-oxo-4H-furo[3,2-c]pyran-3-carboxylate (1b). Compounds 1a and 1b induced micronucleus, mitotic and replication indexes in human lymphocytes (1 and 2 mg/mL). The increases of micronucleus, mitotic and replication indexes show that compounds at high concentrations may become cytotoxic, genotoxic and carcinogenic.

Introduction. Chapter 1. Heavy Metals, Trace Elements and their Cellular Effects. I. Heavy metal toxicity in microbes. Chapter 2. Toxic Metal/Metalloid Tolerance in Fungi - A Biotechnology-Oriented Approach. Chapter 3. Interference of chromium with cellular functions. Chapter 4. Saccharomyces cerevisiae as a Model Organism for Elucidating Arsenic Tolerance Mechanisms. II. Heavy metal induced toxicity in insect cells. Chapter 5 . Heavy Metal Toxicity in an Insect Cell Line (Methyl-HgCl, HgCl2, CdCl2 and CuSO4) . III. Genotoxic effects of heavy metals. Chapter 6. Cellular Changes in Mammalian Cells Induced by Cadmium. Chapter 7. Chromatin toxicity of Ni(II) Ions in K562 Erythroleukemia Cells. Chapter 8. Genotoxic Chromatin Changes in Schizosaccharomyces pombe Induced by Hhexavalent Chromium (CrVI) Ions. Chapter 9. Chromatin Changes upon Silver Nitrate Treatment in Human Keratinocyte HaCaT and K562 Erythroleukemia Cells. IV. Chemical carcinogenesis induced by heavy metals. Chapter 10. Heavy Metal-Induced Carcinogenicity: Depleted Uranium and Heavy Metal. Chapter 11. Role of Oxidative Damage in Metal-Induced Carcinogenesis. V. Cellular responses to heavy metal exposure. Chapter 12. Non-native Proteins as Newly-identified Targets of Heavy Metals and Metalloids. Chapter 13. Cellular Mechanisms to Respond to Cadmium Exposure: Ubiquitin Ligases. Chapter 14. Metals Induced Disruption of Ubiquitin Proteasome System, Activation of Stress Signaling and Apoptosis. VI. Biomakers. Chapter 15. Blood Lead Level (BLL, B-Pb) in Human and Animal Populations: B-Pb as a Biological Marker to Environmental Lead Exposure. VII. Removal of heavy metals. Chapter 16. Removal of Heavy Metal Sulfides and Toxic Contaminants from Water.

This chapter describes the cellular effects of low concentrations of CdCl2 (0.5–5 µM) causing biochemical (strand breaks , carcinogenic indicator, DNA replication, DNA repair) and morphological (chromatin) changes in CHO and murine preB cells. Low Cd concentration (0.5–1 µM) interferes with both replicative and repair DNA synthesis. The replicative DNA synthesis is gradually inhibited, but this inhibition is less than the increment of repair DNA synthesis and the overall rate of DNA synthesis in damaged cells will be higher than in normal cells. This hormesis-like effect suggests the induction of an active DNA repair system. A low level of cell cycle-dependent fluctuation of spontaneous strand breaks was observed in control cells, which was 10–40-times higher in S phase upon Cd treatment. The oxidative DNA damage product 8-oxodeoxyguanosine was induced at low (0.5 µM) CdCl2 concentration. Among the interphase chromatin damages the most characteristic feature was the appearance of holes and disruptions in nuclei which are regarded as typical diagnostic symptoms of cadmium toxicity.

Allium sativum (garlic) has been used since prehistoric times in various cultures as a spice as well as a medicine to combat microbial and fungal infections, help in cardiovascular problems, stimulate immunological system or stop tumor growth. Epidemiological studies indicate that increased consumption of garlic is inversely correlated with the risk of different types of cancer in various human populations. Garlic preparations inhibit chemically induced cancers in animals. This chemo-preventive activity is attributed to organosulfur compounds which modulate Phase I and II detoxification enzymes, thus inhibit pro-carcinogen activation and/or enhance carcinogen neutralization and removal. Laboratory studies also indicate that garlic compounds suppress cancer development at post-initiation phases inducing cell cycle block and apoptosis as well as inhibiting angiogenesis and metastasis. Results of the in vitro studies explain the mechanisms of action of garlic organosulfurs at the molecular level, which is a necessary step before their clinical use for cancer patients. This chapter reviews the evidence on garlic chemo-preventive activities in human populations, animal models and limited clinical trials. It also summarizes the current knowledge on molecular mechanisms of its anti-proliferative activity toward cancer cells, possible interactions with drugs and impact on immune system—factors that should be considered before use of garlic compounds in cancer therapy.

The demand for natural alternatives to prevent enteric cancers especially colonic cancers are increasing. The use of probiotics has attracted much interest due to their long history of safe use and numerous positive clinical evidences. Probiotics are viable microorganisms that confer health benefits to the host once consumed in adequate amounts, primarily by promoting the proliferation of beneficial gastrointestinal indigenous microflora. Various mechanisms have been evaluated on the roles of probiotics in preventing enteric tumour and cancer. Enteric cancers are often induced by carcinogens and mutagens upon prolong or excessive exposures. Probiotics have been found to alleviate the detrimental effects of mutagens and carcinogens leading to reduced colon adenocarcinomas and colon tumour multiplicity. Some mechanisms include the ability of probiotics to reduce the production of b-glucuronidase by pathogenic microflora, absorption of harmful carcinogens, and deactivation of mutagens leading to reduced damage of colonic mucosal cells. Probiotics have also been found to possess systemic anti-neoplastic activities, and thus play a crucial role in the prevention of colorectal cancer. Clinical studies have shown that probiotics could decrease neoplastic transformation via controlling proto-oncogenes and tumour suppressor genes, and via inhibition of pathogens that produce carcinogenic enzymes that form detrimental secondary bile salts, deoxycholic and lithocholic acids. Probiotics have also been associated with reduced mutations of enteric cells caused by DNA damages. One of the largest roles of probiotics lies on their ability to inhibit pathogenic bacteria residing in the colons that release by-products such as superoxide and hydrogen peroxide that could damage the DNA of colonic epithelial cells. Other roles include mucin secretion, bioproduction of conjugated linoleic acid, and the production of short chain fatty acids that modulate the induction of DNA damages. Lesions in the enteric regions of mammals have been reported to progress to tumours and probiotics have been found to decrease the generation of these lesions. Lactobacilli- and bifidobacteria-type probiotics have been found to inhibit the development of aberrant crypt foci, increased plasma total antioxidant potentials, decreased plasma lipid peroxidation, and the inhibition of attaching-effacing lesion formation, that lead to decreased and/or improved incidences of gut lesions.

List of Contributors.- Preface.- 1 Cruciferous Vegetables - and biological activity of isothiocyanates and indoles.- 2 Green Leafy Vegetables in Cancer Prevention.- 3 The Role of Tomato Lycopene in Cancer Prevention.- 4 i -Catotene and Other Carotenoids in Cancer Prevention.- 5 The Role of Alliums and Their Sulphur and Selenium Constituents on Cancer Prevention.- 6 Molecular Mechanisms of Chemoprevention with Capsaicinoids from Chili Peppers.- 7 Influence of Dietary Soy Isoflavones Genistein and Daidzein on Genotoxiciy and Mammary Carcinogenicity in Rats Exposed to the Model Carcinogen 7,12-Dimethylbenz[a] anthracene (DMBA).- 8 The Potential Roles of Seeds and Seed Bioactives on the Prevention and Treatment of Breast and Prostate Cancer.- 9 Nuts as Part of a Whole Diet Approach to Cancer Prevention.- 10 Whole Grains and Their Constituents in Cancer Prevention.- Appendices.- Glossary.- Author Index.- Subject Index.

Continued development of novel munitions for the battlefield opens the possibility of wounds containing embedded fragments of metals or metal mixtures whose toxicological properties may not as yet be well-understood. This chapter reviews what is currently known about two recent additions to many nations’ arsenals: depleted uranium and heavy-metal tungsten alloy . The toxicological and genotoxic properties of these materials, derived from both in vitro and in vivo studies, will be discussed, as will the health effects of known human exposures. Finally, areas requiring further research will be detailed.

Ionizing radiation is a well-established carcinogen in humans and experimental models. While many attribute the increase in cancer risk following ionizing radiation (IR) to DNA damage and subsequent mutations, our experimental data and that of others suggest that ionizing radiation also induces signals that alter multicellular interactions and phenotypes that promote carcinogenesis . Rather than being accessory or secondary to genetic damage, we propose that such radiation effects on stroma and microenvironment create the critical context that promotes cancer development. This review highlights recently described molecular pathways by which stromal cells contribute to cancer and addresses evidence that radiation may act though the microenvironment to promote cancer.

Epidemiological studies provide evidence for the possibility of preventing cancer and/or forestalling the complications of menopause through the consumption of foods containing phytoestrogens such as soy isoflavones. Lifestyle changes in technologically advanced societies, however, limit the consumption of adequate foods to meet health needs; thus supplements of phytoestrogen including soy isoflavones daidzein (DZ) and genistein (GE), considered to be compounds in soy that impart beneficial effects, are ingested in large quantities on a regular basis. This raises health concern since isoflavones are structurally similar to steroidal hormones, and it is possible that they may alter endogenous hormone metabolism and influence the pathogenesis of steroid-dependent diseases such as breast and prostate cancer. Equally important, humans are consistently exposed to mutagenic carcinogens whose toxicities could be enhanced by interaction with ingested isoflavones. Recent report indicates that DZ and GE are not only mutagenic, but also they enhance chemical carcinogenesis in animal models. Here, we report the results of feeding rats with DZ and GE to determine whether the genotoxicity and mammary carcinogenesis induced by the potent rodent mammary carcinogen dimethylbenz[a]anthracene (DMBA) could be altered. The data obtained suggest that DZ and GE diets given separately did not significantly alter DMBA-induced mutagenicity in lymphocytes, liver, mammary and heart, and carcinogenicity in the mammary. The mixture of DZ and GE was effective in reducing DMBA effects, suggesting that consuming diets containing more than one soy isoflavones as opposed to taking supplements in isolation, could impart some benefits; these results are discussed together with other animal studies reported on soy isoflavones.

Chemoprevention is one of the most practical strategies to prevent cancer. Numerous dietary phytochemicals present in fruits, vegetables and spices have been reported to possess cancer preventive properties. Chili peppers are widely consumed spices throughout the world. The non-nutritive pungent phytochemicals present in chili peppers are capsaicinoids. While the principal capsaicinoid from hot chili pepper is a pungent alkaloid capsaicin [(E)-N-(4-hydroxy-3-methoxybenzyl)-8-methyl-6-nonenamide], the major nonpungent vanilloid from sweet red pepper is capsiate [4-hydroxy-3-methoxybenzyl (E)-8-methyl-6-nonenoate]. Both capsaicinoids and capsiates have been shown to possess antioxidant, anti-inflammatory and chemopreventive properties. Biochemical mechanisms underlying chemopreventive effects of capsaicinoids include inhibition of carcinogen activation, stimulation of carcinogen detoxification, attenuation of oxidative and inflammatory responses, inhibition of proliferation, induction of apoptosis in cancer cells, and the blockade of tumor angiogenesis and metastasis. This chapter will focus on the mechanistic aspect of cancer chemoprevention with vanilloids.

Since the previous version of this chapter [1], there have been numerous studies on chloroform (CHC~:J (CAS No. 67-66-3)) in order to explain the mechanism of its action. CHCl3 had detrimental or beneficial effects in various animal studies, depending on the solvent, the species, and the sex of the animals, in addition to other factors. The presence of very small levels of CHCl3 in chlorine-treated water remains a matter for much discussion among environmental groups, the US EPA and the community of toxicologists [2]. The International Agency for Research on Cancer (IARC) considers that there is inadequate evidence for the carcinogenicity of chlorinated drinking water in either animals or humans [3]. A report that weathering of organic matter leads to accumulation of halogenated organic compounds indicates that such occurrences should be considered in risk assessment [4]

Within less than a decade after the discovery of the X-ray by Roentgen, in1895, cancer was recognized to be a late complication of injury by ionizing radiation, and for decades thereafter it was assumed that cancer would result only from doses large enough to cause severe damage of tissue. In the interim, the carcinogenic effects of ionising radiation have been found to vary markedly, depending on the type and anatomical site of the neoplasm in question, the dose, dose rate, and quality of the radiation, the species, genetic background, age, sex, and physiological condition of the exposed subjects, and the potentially modifying influence of exposure to other chemical and physical agents. Individually, moreover, the neoplasms induced by radiation have been found to have no features distinguishing them from those arising from other causes, and with few exceptions they have been detectable only at relatively high doses and dose rates. Consequently, assessment of any risks that may be attributable to low-level irradiation entails the use of models. In this connection, it is noteworthy that although the mechanisms of carcinogenesis remain to be elucidated in detail, the activation of oncogenes, inactivation of tumour-suppressor genes, induction of genomic instability, and effects on other regulatory elements have been implicated in a growing number of instances.

The use of metabolite profiling techniques (metabonomics or metabolomics) in toxicology is a relatively new branch of this science. Due to their unique biochemical properties, cancer cells should, in principle, be an ideal field of application for metabolite profiling. However, due to technical and study design limitations there are only a few reliably metabolite profiles for human tumors. This chapter provides examples for the recognition of metabolic changes in animals induced by exposure to (carcinogenic) chemicals. In two major projects (COMET and MetaMapTox), data bases have been developed which are sufficiently large to evaluate the full potential of metabolite profiling in toxicology and cancer research. In both projects blood and urine were used as matrices which can be easily obtained with minimally-invasive methods. Based on a high degree of standardization and a large-scale controlled data collection, consistent patterns of metabolite changes have been identified which are associated with different toxicological modes of action, some of which are known to enhance tumor development in rodents.

Studies of nanoscale mineral fibers have demonstrated that the toxic and carcinogenic effects are related to the surface area and surface activity of inhaled particles. Particle surface characteristics are considered to be key factors in the generation of free radicals and reactive oxygen species and are related to the development of apoptosis or cancer. Existing physico-chemical methods do not always allow estimation of the nanoparticles impact on organismal and cellular levels. The aim of this study was to develop marker system for evaluation the toxic and carcinogenic effects of nanoparticles on cells. The markers are designed with respect to important nanoparticles characteristics for specific and sensitive assessment of their impact on biological system. We have studied DNA damage, the activity of xanthine oxidoreductase influencing the level of free radicals, bioenergetic status, phospholipids profile and formation of 1H-NMR-visible mobile lipid domains in Ehrlich carcinoma cells. The efficiency of the proposed marker system was tested in vivo and in vitro with the use of C60 fullerene nanoparticles and multiwalled carbon nanotubes. Our data suggest that multiwalled carbon nanotubes and fullerene C60 may pose genotoxic effect, change energy metabolism and membrane structure, alter free radical level via xanthine oxidase activation and cause mobile lipid domains formation as determined in vivo and in vitro studies on Ehrlich carcinoma cells.

Mycotoxin contamination is a worldwide problem and significant economic losses are associated with their impact on human health, animal productivity and both domestic and international trade. The FAO has estimated that up to 25% of the world’s food crops and a higher percentage of the world’s animal feedstuffs are significantly contaminated by mycotoxins and represent a human safety risk. Aflatoxin B1 (AFB1), a potentially lethal metabolite, is a known human carcinogen. AFB1 is toxic to the liver, immunosuppressant, hepatocarcinogenic, teratogenic, and mutagenic. Aflatoxin carryover to animal products poses a health and economic liability and drives the demand for a method to prevent aflatoxin contamination of feedstuffs and/or animal food products such as milk, eggs, and meat. One of the innovative methods to overcome the toxic and carcinogenic effects of AFB1 is to enhance its metabolism by natural substances reportedly possessing hepatoprotective effects. In this study we reported the effect of silymarin, a potent antihepatotoxic agent used as a hepatoprotector in man, on reducing aflatoxin M1 (AFM1) excretion in cows’ milk and the effects of a silymarin in reducing the toxic effects of AFB1 in broiler chickens.