n(7)-hydroxyethylguanine and 7-methylguanine

Endogenous DNA damage is assumed to be a major contributor to aging and cancer. This study compares the steady-state levels of 7-methyl- and 7-(2-hydroxyethyl)-guanine DNA adducts in lymphocytes isolated from the younger (mean age 39.8 years) and the older (mean age 82.8 years) healthy subjects. Using a 32P-post-labelling method, these adducts were measured in lymphocyte DNA from a total of 34 subjects. The results show that the amount of both 7-methyl- and 7-(2-hydroxyethyl)-guanine adducts in the younger age group was similar to that in the older age group. Our findings show that at steady-state the levels of DNA alkylation products are independent of age, suggesting that endogenous DNA damage, through methylation or lipid peroxidation, and the repair of such damage may not be deficient in lymphocytes of older individuals.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Chromatography, High Pressure Liquid; DNA Adducts; DNA Damage; DNA Repair; Guanine; Humans; Lipid Peroxidation; Lymphocytes; Methylation; Middle Aged; Time Factors

Detection of 7-alkylguanine DNA adducts is useful to assess human exposure to and the resulting DNA damage caused by simple alkylating agents. The background 7-methylguanine (7-MG) and 7-hydroxyethylguanine (7-HEG) adduct levels were determined in human and rat tissues, using thin-layer chromatography (TLC) combined with high pressure liquid chromatography (HPLC). In addition, these two adduct levels were also compared in various tissues between smokers and non-smokers. The results demonstrated that the background level of 7-alkylguanine adducts in WBC and lung tissues of non-smokers was 2.9 and 4.0 adducts/107 nucleotides, respectively. In smokers with lung cancers 7-MG adduct level in lung samples (6.3+/-1.9 adducts/107 nucleotides) and in bronchus samples (6.1+/-1.5 adducts/107 nucleotides) was significantly higher than that in WBC samples (3.3+/-0.9 adducts/107 nucleotides). 7-HEG adduct levels obtained from the same individuals were 0.8+/-0.3 in lung, 1.0+/-0.8 in bronchus and 0.6+/-0.2 adducts/107 nucleotides in WBC, respectively. Animal studies showed that background levels of 7-MG (2.1-2.5 adducts/107 nucleotides) in control rats were approximately 2-4-fold higher than 7-HEG levels (0.6-0.9 adducts/107 nucleotides). After a 3-day exposure to 300 ppm ethene, 7-HEG adducts accumulated to a similar extent in different tissues of rats, with the mean adduct level of 5.6-7.0 in liver, 7.4 in lymphocytes and 5.5 adducts/107 nucleotides in kidney.

Topics: Animals; Chromatography, High Pressure Liquid; DNA Adducts; DNA Damage; DNA Methylation; Guanine; Humans; Male; Rats; Rats, Sprague-Dawley

Topics: Alkylating Agents; Carcinogens; Environmental Exposure; Guanine; Humans; Mass Spectrometry