Formation of mutagenic metabolites from benzo( a)pyrene and 2-aminoanthracene by the S-9 fraction from the liver of the Northern pike ( Esox lucius): Inducibility with 3-methylcholanthrene and correlation with benzo[ a]pyrene monooxygenase activity

Abstract

The mutagenicity of benzo[ a]pyrene and 2-aminoanthracene in the Ames test using the S-9 fraction from the liver of the Northern pike ( Esox lucius) was tested. S-9 fractions were prepared both from fish injected intraperitoneally with 3-methylcholanthrene and from control animals. In addition benzo[ a]pyrene monooxygenase activity was assayed in the same S-9 fractions used in the Ames test. S-9 fractions from the liver of the Northern pike were found to convert benzo[ a]pyrene and 2-aminoanthracene to mutagenic metabolites. The number of revertants obtained was increased 2–4-fold in the case of 2-aminoanthracene and 3–14-fold in the case of benzo[ a]pyrene by pretreatment of the pike with a single intraperitoneal injection of 3-methylcholanthrene. This injection also caused a 2–6-fold increase in the benzo[ a]pyrene monooxygenase activity of the S-9 fractions used. These increases in mutagenicity and activity occur mainly during the first 4–12 days after the injection, but further small increases are observed for as long as 60 days. A strong positive correlation was found between the benzo[ a]pyrene monooxygenase activity of the S-9 fractions used and their ability to give rise to revertants in the Ames test using 2-aminoanthracene or benzo[ a]pyrene. This indicates that the major determining factor in the production of reactive metabolites which attack DNA in this in vitro system is the activity of the phase I cytochrome P-450 system.