METABOLISM AND MUTAGENICITY OF 2-ACYLAMINOFLUORENES AND RELATED COMPOUNDS

Abstract

There is a strong association between aromatic hydrocarbon responsiveness and N-hydroxylation of phenacetin, acetanilide, and p-chloroacetanilide in the livers from progeny and the appropriate backcrosses and intercross involving B6 and D2 mice. Mutagenic activity in the Salmonella test system of several 2-acylaminofluorenes were compared using the S-9 liver fractions from B6 and D2 mice. Pretreatment of B6 mice with 3-MC increased the mutagenic activity of all the analogs in the S-9 liver fraction. No increase in mutagenic activity is found in S-9 liver fraction from D2 mice after 3-MC pretreatment, indicating that mutagenic activity correlates with aromatic hydrocarbon responsiveness and N-hydroxylase activity. ANF, an inhibitor of N-hydroxylation of 2-AAF in vitro, inhibits the mutagenic activity of these analogs indicating that N-hydroxylation is the first step in the activation of N-acylaminofluorenes into mutagens.