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

Abstract

The concentration of O 6-ethylguanine (O 6EG) 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 O 6EG was quantitated by optical methods. O 6EG levels in DNA of Clara cell-enriched populations were found to be higher than O 6EG levels in DNA of alveolar type II cell-enriched populations and macrophages following acute DEN treatment. In Clara cell-enriched populations, O 6EG levels found after the 200 mg/kg body wt dose were approximately 50% the levels found after the 100 mg/kg body wt dose, and O 6EG 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. O 6EG accumulated in DNA of Clara cell-enriched populations during subchronic DEN exposure. The differential distribution of O 6EG in target and non-target cell populations suggests the involvement of this promutagenic base in the initiation process of DEN pulmonary carcinogenesis.