Mutagenicity of 1-, 3- and 6-nitrosobenzo[ a]pyrene in Salmonella typhimurium and Chinese hamster ovary cells

Abstract

1-, 3and 6-nitrobenzo[a]pyrene (nitro-BaP) are environmental pollutants (Jager, 1978; Wang et al., 1978; Pitts et al., 1982; Gibson, 1983; PaputaPeck et al., 1983; Schuetzle, 1983) and prototypes of nitro-polycyclic aromatic hydrocarbons (PAHs) derived from carcinogenic parent PAHs. All three compounds are S9-mediated mutagens in the Salmonel la t y p h i m u r i u m reversion assay, while 1and 3-nitro-BaP are also potent mutagens without exogenous activation (Tokiwa et al., 1981; Campbell et al., 1981; Fu et al., 1982; Pitts et al., 1982, 1984; Chou et al., 1984, 1985, 1986; Lofroth et al., 1984; Hass et al., 1986a). The direct mutagenic activities are thought to be due to enzymatic reduction of the nitro substituents, since a Salmonella tester strain that is deficient in a major component of the bacterial nitroreductase system, TA98NR, is highly resistant to the mutagenic effects of 1and 3-nitro-BaP (Pitts et al., 1984; Chou et al., 1985, 1986; Hass et al., 1986a). Also, the immediate nitro reduction products of 1-, 3and 6-nitro-BaP, 1-, 3and 6-nitrosobenzo[a]pyrene (nitroso-BaP) are mutagenic in Salmonella (Fu et al., 1988a; Thornton-Manning et al., in preparation), land 3-nitro-BaP are also S9-mediated mutagens in Chinese hamster ovary (CHO) cells, but none of the nitro-BaPs displays any direct mutagenic activity in these cells (Hass et al., 1986b; ThorntonManning et al., 1988). Although reduction of 1and 3-nitro-BaP has been demonstrated using mammalian enzymes (Chou et al., 1985, 1986; Colvert and Fu, 1986), it has been suggested that CHO cells lack the capacity to perform these reactions (Hass et al., 1986b). In order to further elucidate the metabolism involved in the mutagenic responses produced by the nitro-BaPs, the mutagenicity of 1-, 3and 6-nitroso-BaP was determined in the CHO cell assay and in strains of Salmonella which differ in nitroreductase and Oacetylase activity.