DNA ethylation in target and non-target organs of hamsters and rats treated with diethylnitrosamine

Abstract

Kinetics of ethylation of target and non-target organ DNA in vivo by diethylnitrosamine (DEN) was compared in rats and Syrian golden hamsters, since published reports indicate a single dose of DEN induces both kidney and liver tumors in rats and almost exclusively respiratory tract tumors in hamsters. Following treatment with 200 mg DEN/kg, 7-ethylguanine (7-etG) was lost more rapidly from hamster than from rat liver DNA, while O 6 -ethylguanine (O 6 -etG) persisted longer in hamster than in rat liver DNA. DNA ethylation was not detected in rat lung (non-target organ), while both 7-etG and O 6 -etG were quantitated in hamster lung (target organ) following DEN treatment. DNA ethylation in rat kidney DNA was ∼ 1 10 of that in liver by 200 mg DEN/kg, and the persistence of 7 -etG and O 6 -etG differed only slightly in these tissues. Ethylation of hamster liver DNA by DEN at doses between 20 and 200 mg/kg, as measured by 7 -etG and O 6 -etG was proportional to the dose of carcinogen up to 160 mg/kg; at larger doses DNA ethylation sharply increased. Differences in the persistence of O 6 -etG between DEN-treated rats and hamsters cannot solely account for species differences in the organotropism of DEN carcinogenesis.