Biological actions of nitroarenes in short-term tests on Salmonella, cultured mammalian cells and cultured human tracheal tissues: possible basis for regulatory control.

Abstract

Pure synthetic nitropyrene compounds were subjected to a mutation test using Salmonella typhimurium TA 98 and TA 100 with and without S9 mix, a metabolic activation system. Dinitropyrenes were highly mutagenic. Among them, 1,8-dinitropyrene was the most potent mutagen, producing 940,000 revertants of TA 98/micrograms. 1,3,6-Trinitropyrene and 1,3,6,8-tetranitropyrene were also highly mutagenic, producing 708,000 and 221,000 revertants/micrograms, respectively. 1-Nitropyrene was weakly mutagenic. All nitropyrenes were more mutagenic towards TA 98 than TA 100, and all mutagenic activities were abolished by the presence of S9 mix. Di- and trinitropyrenes were demonstrated to be mutagenic to Chinese hamster lung cells without metabolic activation, by using diphtheria toxin resistancy as a marker. The range of mutagenic potential of nitropyrenes was much narrower with cultured mammalian cells than with Salmonella. 1-Nitropyrene was not mutagenic. 1,6-Dinitropyrene and 1-nitropyrene induced unscheduled DNA synthesis in epithelial cells of in vitro cultured human bronchi, as did diol-epoxides of benzo[a]pyrene, while benzo[a]pyrene itself was inert. 1-Nitropyrene and 3-nitrofluoranthene produced subcutaneous fibrosarcomas at the loci of injections in the backs of rats. Tumors were found in 47% and 40% of animals with total doses of 40 mg of 1-nitropyrene and 30 mg of 3-nitrofluoranthene, respectively. The biomedical significance of nitroarenes is discussed.