Formation and accumulation of O6-ethylguanine in DNA of enriched populations of Clara cells, alveolar type II cells, and macrophages of hamsters exposed to diethylnitrosamine.
The concentration of O6-ethylguanine (O6EG) in DNA of enriched populations of hamster Clara cells, alveolar type II cells, and macrophages was determined following acute diethylnitrosamine (DEN) exposure, 100 and 200 mg/kg body wt, and during subchronic DEN exposure, 20 mg/kg body wt, 2 times/week. Pulmonary cells were separated by centrifugal elutriation. DNA was collected on polycarbonate filters and hydrolyzed by mild acid. Purines bases were separated by high-pressure liquid chromatography, and O6EG was quantitated by optical methods. O6EG levels in DNA of Clara cell-enriched populations were found to be higher than O6EG levels in DNA of alveolar type II cell-enriched populations and macrophages following acute DEN treatment. In Clara cell-enriched populations, O6EG levels found after 200 mg/kg body wt dose were approximately 50% the levels found after the 100 mg/kg body wt dose, and O6EG levels found at 24 h post-treatment were approximately 50% the levels found at 12 h post-treatment for both the 100 and 200 mg/kg body wt doses. O6EG accumulated in DNA of Clara cell-enriched populations during subchronic DEN exposure. The differential distribution of O6EG in target and non-target cell populations suggests the involvement of this promutagenic base in the initiation process of DEN pulmonary carcinogenesis.
D000478:Alkylation; D000818:Animals; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004052:Diethylnitrosamine / Q000633:toxicity*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D004052:Diethylnitrosamine; C007673:6-ethylguanine; D006147:Guanine; D004247:DNA