Endogenous and background DNA adducts by methylating and 2-hydroxyethylating agents

Abstract

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/10 7 nucleotides, respectively. In smokers with lung cancers 7-MG adduct level in lung samples (6.3±1.9 adducts/10 7 nucleotides) and in bronchus samples (6.1±1.5 adducts/10 7 nucleotides) was significantly higher than that in WBC samples (3.3±0.9 adducts/10 7 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/10 7 nucleotides in WBC, respectively. Animal studies showed that background levels of 7-MG (2.1–2.5 adducts/10 7 nucleotides) in control rats were approximately 2–4-fold higher than 7-HEG levels (0.6–0.9 adducts/10 7 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/10 7 nucleotides in kidney.