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.

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 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.