2-aminofluorene-hepatic DNA adducts in congenic mouse lines differing in Ah responsiveness.
The influence of beta-naphthoflavone (BNF) pretreatment on 2-aminofluorene (2-AF)-hepatic DNA adduct formation was evaluated in Ah-responsive and non-responsive congenic mouse lines through use of HPLC analysis of 32P-postlabeled nucleotides. C57BL/6J (B6) mice were used as an example of BNF-responsive mice while B6.D-Ahd, a line congenic with B6, was used as the non-responsive line. Induction at the Ah locus with BNF increased adduct levels in hepatic DNA in B6 mice but not in B6.D mice 3 h after a 60 mg/kg i.p. dose of 2-AF. The slow acetylator counterparts of B6 and B6.D, namely B6.A and B6.A.D-NatsAhd (a new congenic line produced from B6.A and B6.D), had lower adduct levels than the rapid acetylators before induction. Although adduct levels in B6.A and B6.A.D were increased following BNF induction, the level of adducts remained below those of induced B6 mice. In the three lines that responded to BNF induction, male mice had a greater relative increase in hepatic DNA adduct levels than females. For all four lines, with or without BNF pretreatment, greater adduct levels were found in the females. These results imply that responsiveness to aromatic hydrocarbon induction, as well as rapid acetylation, may be risk factors in hepatic DNA damage following arylamine exposure. Female mice appear to be more susceptible to such damage than males.
Levy
G N
GN
Department of Pharmacology, University of Michigan, Ann Arbor 48109.
Weber
W W
WW
D000107:Acetylation; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005449:Fluorenes / Q000378:metabolism*; D005838:Genotype; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D011292:Premedication; D012727:Sex Characteristics; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D005419:Flavonoids; D005449:Fluorenes; C012177:2-aminofluorene; D019324:beta-Naphthoflavone; D004247:DNA