MUTAGENESIS OF CERTAIN BENZO[A]PYRENE PHENOLS INVITRO FOLLOWING FURTHER METABOLISM BY MOUSE-LIVER

Low concentrations of 1-hydroxy- and 3-hydroxybenzo[a]pyrene in the presence of NADPH and liver S-9 fraction from 3-methylcholanthrene-treated C57BL/6N mice are as much as 3-fold more mutagenic than benzo[a]pyrene in the bacteria Salmonella typhimurium LT2 tester strain TA98. The level of mutagenicity rises with increasing phenol or S-9 protein concentration. In this system, 9-hydroxy-benzo[a]pyrene is slightly mutagenic, while 2-hydroxy-, 7-hydroxy- and 12-hydroxybenzo[a]pyrene are not mutagenic at low concentrations. The S-9 fraction from 3-methylcholanthrene-treated DBA/2N mice or phenobarbital-treated C 5 7BL/6N mice does not support significant levels of mutagenesis. The high level of mutagenicity by 1-hydroxy- or 3-hydroxybenzo[a]pyrene is inhibited by α-naphthoflavone but is not inhibited by metyrapone, 1, 2-epoxy-3, 3, 3-trichloropropane or glutathione. The substrate for UDP-glucuron-osyltransferase, UDP-glucuronic acid, prevents more than half of the mutagenicity caused by the further metabolism of 1-hydroxy- and 3-hydroxybenzot alpyrene. The combination of UDP-glucuronic acid and UDP-N-acetylglucosamine provides an even higher level of protection. The addition of the substrate for sulfotransferase(s), 3'-phosphoadenosine 5'-phosphate sulfate, also prevents about half of the mutagenesis caused by 1-hydroxy- or 3-hydroxybenzo[a]pyrene. © 1979.