MUTAGENICITY OF MONONITROPYRENES AND DINITROPYRENES IN THE SALMONELLA-TYPHIMURIUM-TM677 FORWARD MUTATION ASSAY

Nitropyrenes are a group of widespread environmental pollutants, some of which are highly potent as bacterial and mammalian cell mutagens an d as animal carcinogens. A quantitative bacterial forward mutation ass ay, based on resistance to 8-azaguanine (8-AG) in Salmonella typhimuri um TM677, was employed as an alternative to reversion assays to reexam ine the mutagenicity of 1-, 2-, and 4-nitropyrene (1-, 2-, and 4-NP) a nd 1,3-, 1,6-, and 1,8-dinitro-pyrene (1,3-, 1,6-, and 1,8-DNP) in the presence and absence of rat liver postmitochondrial supernatant (PMS) . The major finding is that 2-NP, reported as a potent mutagen in the absence of PMS in bacterial reversion assays, was inactive in the abse nce of PMS in this assay. However, 2-NP was mutagenic in the presence of PMS. The implications of this observation with respect to sample pu rity and the metabolism of 2-NP are discussed. Without PMS the followi ng minimum detectable mutagen concentration (MDMC) potency series expr essed as nmol/ml was obtained: 1,8-DNP (0.5 x 10(-3)), 1,6-DNP (1.2 x 10(-3)), 1,3-DNP (2.3 x 10(-3)), 4-NP (0.2), 1-NP (0.2), 2-NP(> 1200), pyrene(> 1500). With PMS the potency series was: 1,6-DNP (0.7), 1,8-D NP (2.1), 4-NP (2.2), 2-NP (2.6), 1,3-DNP (3.7), 1-NP (4.6), pyrene (> 1500). With the exception of 2-NP, all the nitropyrenes were more muta genic without PMS than with PMS. The greatest difference was observed with the dinitropyrenes, which were three orders of magnitude less pot ent in the presence of PMS. Pyrene, often reported as a bacterial muta gen in the presence of PMS, was nonmutagenic in this assay when a puri fied sample was tested.