7-methylguanine and Body-Weight

Urinary 8-hydroxydeoxyguanosine (8-OH-dG) and 7-methylguanine (m7Gua) were measured by a column-switching high performance liquid chromatography method as markers of oxidative and methylating DNA damage, respectively. We investigated the associations between urinary 8-OH-dG or m7Gua and various lifestyle and demographic factors, such as age and sex. The urinary 8-OH-dG excretion level was positively correlated with cigarette smoking, but inversely correlated with fruit consumption, physical activity and total energy consumed per day. A multiple regression analysis revealed that daily physical activity and healthy meal combinations decreased the urinary 8-OH-dG level, whereas alcohol consumption increased it. In terms of the urinary m7Gua measurement, cigarette smoking, age and consumption of meat, fish, egg, soybean, etc. were positively correlated with the urinary m7Gua level, whereas body weight, BMI, physical activity, and dietary index score, which indicates good nutritional balance, were negatively correlated with the amount of m7Gua. Based on a multiple regression analysis, cigarette smoking and age correlated with the m7Gua level, while high BMI and healthy meal combinations have significant reducing effects on m7Gua level. Therefore, the urinary m7Gua level is considered to be a useful marker of DNA methylation, not only from smoking, but also from aging and unhealthy dietary habits.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Age Factors; Alcohol Drinking; Biomarkers; Body Mass Index; Body Weight; Chromatography, High Pressure Liquid; Deoxyguanosine; Exercise; Feeding Behavior; Guanine; Humans; Life Style; Male; Middle Aged; Regression Analysis; Sensitivity and Specificity; Smoking; Surveys and Questionnaires; Young Adult

Dimethyl sulfate (DMS) is an alkylating agent that is carcinogenic to the respiratory tract of rodents. DNA adducts, cell proliferation, and histopathology were assessed in rats to better understand the molecular dosimetry and tissue dynamics associated with repeated inhalation exposure to DMS. For DNA methylation, rats were exposed to DMS vapor 6 h/day for up to 10 days to 0.0, 0.1, 0.7 and 1.5 ppm. N7-Methylguanine and N3-methyladenine were detected in neutral thermal hydrolysates of DNA isolated from respiratory tract tissues by high-performance liquid chromatography (HPLC) using fluorescence and ultraviolet (UV) detection. DNA methylation was greatest in DNA isolated from nasal respiratory mucosa, less in olfactory, and little was found in lung. N7-Methylguanine levels in respiratory mucosa approached steady-state levels by day 5, and N7-methylguanine persistence following exposure for 5 consecutive days was also determined. Loss of N7-methylguanine from respiratory and olfactory mucosa appeared to follow first-order kinetics. N3-Methyladenine levels were at or below detection limits in all samples. The effect of DMS on histopathology and cell proliferation in the nasal epithelium was also investigated. Rats were exposed nose-only for 2 wk to DMS vapor at concentrations of 0, 0.1, 0.7, or 1.5 ppm. Inhalation exposure to DMS induced degenerative and inflammatory changes in nasal epithelium at >or=0.7 ppm. Cell proliferation evaluations showed a trend towards an increased response at 1.5 ppm. These experiments demonstrate that DMS can induce cytotoxic and proliferative effects and is a potent methylating agent of the nasal mucosa in vivo. These experiments will provide data for the development of dosimetry models useful for risk extrapolation.

Topics: Adenine; Administration, Inhalation; Alkylating Agents; Animals; Body Weight; Cell Proliferation; DNA; DNA Adducts; DNA Methylation; Guanine; Male; Methylation; Models, Biological; Mutagens; Olfactory Mucosa; Purines; Rats; Risk; Sulfuric Acid Esters

Topics: Animals; Body Weight; Creatinine; Guanine; Male; RNA; RNA, Messenger; Social Isolation; Stress, Psychological; Tupaia

In our search for new non-invasive methods to determine metabolic and nutritional state, we have identified several specific, modified, urinary one-way catabolites of rRNA, tRNA and mRNA which permit the assessment of the whole-body turnover of these RNA classes. A comparison of the steady-state turnover of RNA and the proteins actin plus myosin (determined using urinary 3-methylhistidine) in preterm infants and adults showed that preterm infants have about 3 times higher average turnover rates per unit body weight than adults of tRNA and rRNA as well as of actin plus myosin, whereas calculated mRNA turnover was 6 times higher in preterm infants than in adults. These as well as our recent observations of RNA turnover in different mammals are compared here with data on whole-body protein turnover and basal metabolic rates (BMR) in different mammalian species including man, for which data are available. The turnover rates of tRNA, rRNA, protein and energy (BMR) can be described by the relation, turnover = const. x body mass (exp.), the extrapolated exponents being 0.69-0.78. This suggests a common underlying principle, possibly energy turnover, as cause for the coordinated whole-body turnover rates of RNA and protein in the steady state.

Topics: Adult; Animals; Basal Metabolism; Body Weight; Child; Chromatography, High Pressure Liquid; Creatinine; Cricetinae; Female; Guanine; Humans; Infant, Newborn; Male; Methylhistidines; Mice; Muscle Proteins; Nutritional Status; Proteins; Rats; RNA