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Free radicals and other reactive oxygen or nitrogen species are constantly generated in vivo and can cause oxidative damage to DNA. This damage has been implicated to be important in many diseases, including cancer. The assessment of damage in various biological matrices, such as tissues, cells, and urine, is vital to understanding this role and subsequently devising intervention strategies. During the last 20 years, many analytical techniques have been developed to monitor oxidative DNA base damage. High-performance liquid chromatography-electrochemical detection and gas chromatography-mass spectrometry are the two pioneering contributions to the field. Currently, the arsenal of methods available include the promising high-performance liquid chromatography-tandem mass spectrometry technique, capillary electrophoresis, 32P-postlabeling, antibody-base immunoassays, and assays involving the use of DNA repair glycosylases such as the comet assay. The objective of this review is to discuss the biological significance of oxidative DNA damage, evaluate the effectiveness of several techniques for measurement of oxidative DNA damage in various biological samples and review current research on factors (dietary and non-dietary) that influence DNA oxidative damage using these techniques. [ABSTRACT FROM AUTHOR]

Since tomato consumption is associated with decreased risk of prostate cancer, cell proliferation, cell cycle progression and apoptosis by LNCaP human prostate cancer cells might elucidate action of tomatoes. To discover possible bioactive fractions of tomatoes, whole tomato paste and its water and hexane extract were used and biomarkers of carcinogenesis were measured. After 6, 24 and 48 hr of incubation, cells were harvested and determined cell growth. Tomato paste hexane extract inhibited cell proliferation by 33% compared to the control after 48 hr incubation. Whole tomato paste and its water extract showed only modest growth inhibition. Tomato paste hexane extract at 5 μM lycopene increased G_2/M-phase of the cell cycle from 13 to 28% and decreased S-phase cells from 45 to 29%. Apoptosis was observed at the 5 μM hexane extract at the late stages during 24 and 48 hr treatment. Tomato, therefore, deserves study as a potential chemopreventive/chemotherapeutic agent. [ABSTRACT FROM AUTHOR]

Animal and epidemiological studies point to a cancer preventive/therapeutic role for tomato products and its antioxidant, lycopene. It is hypothesized that lycopene will behave as an antioxidant at low concentrations and as a prooxidant at high concentrations in LNCaP human prostate cancer cell culture systems. We characterized the antioxidant, and prooxidant effects of a hexane extract of tomato paste (TP) and water solublized lycopene at different concentrations using a prostate cancer cell line. Placebo (5% triglyceride, Roche Inc.) was used as a control. After 6, 24 hr and 48 hr incubation, LNCaP cells were harvested and used for each measurement. Cellular proliferation was determined using the MTT colorimetric assay. Lycopene and TP hexane extract inhibited cell growth in a dose-dependent (0.1–50 μM lycopene) manner and growth inhibition was 55% and 35% at 1 μM lycopene and TP hexane extract, respectively after 48 hr incubation. The levels of 8-hydroxydeoxyguanosine/deoxyguanosine (an oxidative DNA damage product) was significantly increased starting at 5 μM lycopene from both TP hexane extract and pure lycopene after 24 and 48 hr incubation with no protection at the lower concentrations. Malondialdehyde formation (a lipid peroxidation product measured by HPLC separation of the MDA-TBA adduct) was significantly reduced at low concentrations (0.1–1 μM) of lycopene in all treatments. Clinically relevant concentrations of lycopene and the tomato fraction containing lycopene significantly reduced LNCaP cancer cell survival which can only be partially explained by increased DNA damage at high lycopene concentrations (> 5 μM). Low concentrations of lycopene acted as a lipid antioxidant but did not protect DNA. [ABSTRACT FROM AUTHOR]

Assesses the oxidative DNA damage in prostate cancer patients consuming tomato sauce-based foods. Accumulation of lycopene in the prostate tissue; Analysis of lycopene concentration in tomato sauce; Method and design of the study.

Two previous studies have shown higher circulating gastrin levels in subjects with colonic neoplasia than in colonoscopy-negative controls. In this much larger study, sera were collected from fasting subjects undergoing colonoscopy. Colonoscopy with biopsy classified participants as having colonic adenomas (N = 139), colon carcinomas (N = 29), or controls without colonic neoplasia (N = 150). Frozen, stored sera were later analyzed for gastrin by radioimmunoassay. Serum gastrin values were no higher in subjects with colonic adenomas or carcinoma than in colonoscopy-negative controls. We conclude that elevated serum gastrin levels play little, if any, role in the initiation of colonic neoplasia. [ABSTRACT FROM AUTHOR]

In vitro studies suggest that insulin-like growth factor I (IGF-I) may modulate hepatic production and peripheral utilization of lipoproteins. We measured blood concentrations of IGF-I; total, high-density-lipoprotein, and low-density-lipoprotein (LDL) cholesterol; and apolipoproteins in 18 women with above average cholesterol after high- and low-fat diet periods. Total cholesterol fell 6% (P < 0.02) during the low-fat diet because of reduced concentrations of LDL cholesterol (P < 0.01). Serum concentrations of IGF-I were inversely correlated with total and LDL cholesterol and apolipoprotein B during both high-fat (r = -0.676, P < 0.005; r = -0.745, P < 0.001; and r = -0.504, P < 0.04, respectively) and low-fat (r = -0.656, P < 0.005; r = -0.757, P < 0.001; and r = -0.695, P < 0.001, respectively) diets. IGF-I increased with reduced fat intake in obese subjects only. Thus, IGF-I may contribute to the regulation of LDL cholesterol in mildly hypercholesterolemic women but may not mediate the beneficial response to reduced fat intake. [ABSTRACT FROM AUTHOR]

The effect of a nutritionally complete liquid-formula diet without soy polysaccharide or with the fiber source at 20, 30, or 40 g/d on mineral retention in young men was examined. Addition of 20 g soy polysaccharide to the liquid formula significantly (p < 0.05) improved the retentions of copper, iron, zinc, and magnesium over the diet without added fiber. The highest level of soy polysaccharide (40 g/d) resulted in significantly (p < 0.05) lower Cu, Zn, Fe, and Mg retentions than did the 20-g diet and the 30-g diet had an intermediate effect. Except for slightly negative Cu (-0. 1 ± 0.4 mg) and Fe (-0.6 ± 3.7 mg) retentions on the 40-g diet, retentions of all minerals remained positive throughout the study. The liquid-formula diet supplemented with 40 g soy polysaccharide could have a deleterious effect on mineral retentions in persons consuming the diet as their sole nutritional source. [ABSTRACT FROM AUTHOR]

The article focuses on the selection of surrogate endpoint biomarkers to evaluate the efficacy of lycopene/tomatoes for the prevention/progression of prostate cancer. The use of surrogate endpoint biomarkers (SEBs) is essential to the crafting of cost-effective clinical trials to evaluate not only the efficacy of lycopene/tomatoes but also combinations of bioactive compounds. The closer the SEB is in the pathway to prostate cancer expression or progression, the more likely its predictive value. High-grade prostate intraepithelial neoplasia, microvessel density, and prostate-specific antigen have been exploited for these purposes, and their sensitivity and specificity in predicting clinically relevant prostate cancer can be determined. The pathways modulated by tomato bioactive ingredients can be determined through tissue culture and animal studies. A number of possible bioactive compounds are contained in tomato. consumption. Lycopene and quercetin are the likeliest candidates for prostate cancer mediation. They are predominant compounds in tomato and have been shown in animal studies to reduce cancer.

The article offers the response of the editor to the commentaries on the investigation related to the prevention of Alzheimer disease. It tackles the suggestion of the U.S. National Institutes of Health (NIH) on the contributions of estrogen and progesterone to the disease. It states that there is no clinical recommendations for hormone therapy that can be made with respect to the prevention of the disease.

Objective: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on prevention of Alzheimer's disease and cognitive decline., Participants: A non-Department of Health and Human Services, nonadvocate 15-member panel representing the fields of preventive medicine, geriatrics, internal medicine, neurology, neurological surgery, psychiatry, mental health, human nutrition, pharmacology, genetic medicine, nursing, health economics, health services research, family caregiving, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience., Evidence: Presentations by experts and a systematic review of the literature prepared by the Duke University Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience., Conference Process: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government., Conclusions: Cognitive decline and Alzheimer’s disease are major causes of morbidity and mortality worldwide and are substantially burdensome to the affected persons, their caregivers, and society in general. Extensive research over the past 20 years has provided important insights on the nature of Alzheimer’s disease and cognitive decline and the magnitude of the problem. Nevertheless, there remain important and formidable challenges in conducting research on these diseases, particularly in the area of prevention. Currently, firm conclusions cannot be drawn about the association of any modifiable risk factor with cognitive decline or Alzheimer’s disease. Highly reliable consensus-based diagnostic criteria for cognitive decline, mild cognitive impairment, and Alzheimer’s disease are lacking, and available criteria have not been uniformly applied. Evidence is insufficient to support the use of pharmaceutical agents or dietary supplements to prevent cognitive decline or Alzheimer’s disease. We recognize that a large amount of promising research is under way; these efforts need to be increased and added to by new understandings and innovations (as noted in our recommendations for future research). For example, ongoing studies including (but not limited to) studies on antihypertensive medications, omega-3 fatty acids, physical activity, and cognitive engagement may provide new insights into the prevention or delay of cognitive decline or Alzheimer’s disease. This important research needs to be supplemented by further studies. Large-scale population-based studies and randomized controlled trials (RCTs) are critically needed to investigate strategies to maintain cognitive function in individuals at risk for decline, to identify factors that may delay the onset of Alzheimer’s disease among persons at risk, and to identify factors that may slow the progression of Alzheimer’s disease among persons in whom the condition is already diagnosed.

Background: The purpose of this study was to determine the course of oxidative stress in trauma patients as measured by antioxidant disappearance and modulation of DNA damage. The study also explored the role of injury severity and the effect of changes in plasma lipoprotein concentration as the result of hemodilution on lipid-soluble plasma antioxidant concentrations., Methods: The study population included 17 adult male trauma patients in an urban level-1 trauma hospital and 12 healthy adult male controls. Blood was collected immediately after admission in the emergency room, and on days 2, 3, 4, 6, and 8 of admission. Plasma antioxidant concentrations and total cholesterol concentrations were evaluated. DNA damage was evaluated using the ratio of 8-hydroxydeoxyguanosine to deoxyguanosine (8OhdG to dG). Admission data were compared with data from controls., Results: Plasma antioxidant concentrations (except alpha-tocopherol) significantly decreased by 9.9% to 34.3% in the 24 hours after trauma and remained depressed throughout day 8. Repeated measures regression analysis for trend showed a significant increase in unadjusted alpha-tocopherol from day 1 to day 8 (p < .008). No other unadjusted antioxidant or plasma cholesterol showed a significant change. After individually adjusting antioxidant concentrations by total cholesterol, only gamma-tocopherol (22.2%) and lycopene (22.6%) were decreased (p < .04) in the 24 hours after trauma. Repeated measures regression analysis for trend for the cholesterol-adjusted antioxidants showed a significant decrease from day 1 to day 8 for cholesterol-adjusted alpha-carotene (p < .007) and beta-carotene (p < .007). Trauma patients were divided into more and less severely injured groups based on Injury Severity Score (ISS). Decreases in antioxidant concentration from day 1 to day 2 were found for the patients in the more injured group, with no significant differences from day 1 to day 2 in the less severely injured group. Cholesterol-adjusted gamma-to copherol (29.7%, p < .003) and lycopene (32.7%, p < .05) decreased from day 1 to day 2 in the more severely injured group. Using repeated measures regression analysis for trend, the only antioxidant that was significantly different in the high versus low ISS groups from day 1 through day 6 was cholesterol-adjusted lutein-zeaxanthin (p < .02). Compared with controls, trauma patients had significantly lower (27.3% to 64.9%) concentrations of all cholesterol-adjusted antioxidants at day 1 except for lycopene. Trauma patients had higher leukocyte 8OhdG to dG ratios at admission (42.6%, p < .05), but 8OhdG to dG ratios tended to decrease over the 24 hours after trauma (p < .07). This decrease was greater in the 3 trauma patients with an admission 8OhdG to dG ratio greater than 6 x 10(-5) (59.3% versus 0.05%, p < .03)., Conclusions: The difference in antioxidant concentrations between trauma patients and controls may have been associated with oxidative stress or with a poorer diet. The difference between antioxidant concentrations and cholesterol-adjusted antioxidant concentrations is likely caused by hemodilution or by changes in plasma lipid levels as a result of trauma. Therefore, individually adjusting lipid-soluble antioxidant concentrations by total cholesterol concentrations is important in trauma patients. Leukocyte 8OhdG to dG ratios were already elevated in trauma patients on admission but returned nearly to control levels 24 hours later, indicating short-term responsiveness to DNA oxidation in trauma patients and an extensive capacity for DNA repair within 24 hours.

Several epidemiological studies suggest a lower incidence of prostate cancer in men who routinely consume tomato products. Tomatoes are the primary dietary source of lycopene, which is among the most potent antioxidants of the carotenoids. Men with clinical stage T1 or T2 prostate adenocarcinoma were recruited (n = 32) and consumed tomato sauce based pasta dishes for 3 weeks (equivalent to 30 mg of lycopene per day) before radical prostectomy. Prostate tissue from needle biopsy just before intervention and prostectomy after supplementation from a subset of 11 subjects was evaluated for both total lycopene and lycopene geometrical isomer ratios. A gradient HPLC system using a C(18) column with UV-vis absorbance detection was used to measure total lycopene. Because the absorbance detector was insufficiently sensitive, HPLC with a C(30) column and positive ion atmospheric pressure chemical ionization mass spectrometric (LC-MS) detection was developed as a new assay to measure the ratio of lycopene cis/trans isomers in these samples. The limit of detection of the LC-MS method was determined to be 0.93 pmol of lycopene on-column, and a linear response was obtained over 3 orders of magnitude. Total lycopene in serum increased 2.0-fold from 35.6 to 69.9 microg/dL (from 0.664 to 1.30 microM) as a result of dietary supplementation with tomato sauce, whereas total lycopene in prostate tissue increased 3.0-fold from 0.196 to 0.582 ng/mg of tissue (from 0.365 to 1.09 pmol/mg). all-trans-Lycopene and at least 14 cis-isomer peaks were detected in prostate tissue and serum. The mean proportion of all-trans-lycopene in prostate tissue was approximately 12.4% of total lycopene before supplementation but increased to 22.7% after dietary intervention with tomato sauce. In serum there was only a 2.8% but statistically significant increase in the proportion of all-trans-lycopene after intervention. These results indicate that short-term supplementation with tomato sauce containing primarily all-trans-lycopene (83% of total lycopene) results in substantial increases in total lycopene in serum and prostate and a substantial increase in all-trans-lycopene in prostate but relatively less in serum.