MUTAGENICITY OF THE ATMOSPHERIC TRANSFORMATION PRODUCTS 2-NITROFLUORANTHENE AND 2-NITRODIBENZOPYRANONE IN SALMONELLA AND HUMAN CELL FORWARDMUTATION ASSAYS

The mutagenicity of the atmospheric transformation products 2-nitroflu oranthene (2-NF) and 2-nitrodibenzopyranone (2-NDBP), as well as a rel ated isomer 3-nitrodibenzopyranone (3-hTDBP), was measured in quantita tive forward mutation assays with bacteria (Salmonella typhimurium TM6 77) and in two metabolically competent human cell lines (MCL-5 and h1A 1v2) that differ in their complement of cytochrome P350s and microsoma l epoxide hydrolase. 2-NF was a potent mutagen in Salmonella TM677 bot h in the absence and presence of rat liver postmitochondrial supernata nt (PMS). 2-NDBP was non-mutagenic in the absence of PMS, but was muta genic in its presence. The converse result was obtained for 3-NDBP. Th e mutagenic potency series in Salmonella in the absence of PMS, expres sed as the minimum detectable mutagen concentration (MDMC) in nmol/ml, was: 2-NF, 2.5; 3-NDBP, 16.9; and 2-NDBP, > 415. With PMS, the potenc y series was: 2-NF, 1.2; 2-NDBP, 15.1; and 3-hTDBP, 208. Neither 2-NDB P nor 3-NDBP were mutagenic at the tk locus in MCL-5 or h1A1v2 cells a t up to 200 nmol/ml. 2-NF was also inactive in MCL-5 cells, but was a potent mutagen in h1A1v2 cells with an MDMC of 0.02 nmol/ml. Cytochrom e P450 CYP1A1, present constitutively only in h1A1v2 cells, was implic ated in 2-NF activation because mutagenicity was reduced by 55-80% whe n alpha-naphthoflavone (ANF) was present during incubation. The lack o f mutagenicity in MCL-5 cells was attributed to the inability of 2-NF to induce CYP1A1 activity in this cell line. These data indicate a pri mary role for ring oxidation in 2-NF activation. Previous emphasis pla ced upon 2-NDBP as a major mutagen in ambient air may need to be modif ied in view of the negative results for this compound in the human fal l assays and in the absence of PMS in Salmonella TM677. However, these findings support the concern that 2-NF may be a risk to human health.