芳香族炭化水素ニトロ誘導体の変異原性, 発がん性とその危険度

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  • Mutagenicity and Carcinogenicity of Nitrated Polycyclic Aromatic Hydrocarbons

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New nitrated polycyclic aromatic hydrocarbons including dinitropyrenes (diNPs), dinitrofluoranthenes (di-NFs), and dinitrobenzo (a) pyrenes (diNBPs), were discovered and were tested for mutagenic and carcinogenic action.<BR>The diNPs 1, 3-, 1, 6-and 1, 8-diNP mutated Salmonella typhimurium his-TA98 at the frequencies of 81.4 to 261 revertants per pmol, and were widely distributed in diesel emission particulates and airborne materials as the major mutagen. Rats given 1, 6-and 1, 8-diNP significantly induced malignant fibrous hystiocytomas in the local site by subcutaneous injection.<BR>In addition, 3, 7-and 3, 9-diNF discovered were potent mutagen in the Salmonella microsome assay system, and carcinogen in the lungs of rats. The lungs of rats given each compound significantly induced squamous cell carcinoma at the minimum dose level of 50 μg per rat. It was also found that both compounds induced micronuclear polychromatic erythrocytes in the femoral marrow cells in mice. These results suggest induction of chromosome aberrations or chromosome damage.<BR>There was a relationship between NO2-substitution of benzo (a) pyrene (BP) and the mutagenic potency of nitro-BPs. The nitrated BP substituted at the 3 position onthe chemical structure of BP was quickly reduced by rat liver microsomes in the presence of NADPH or NADP as a cofacter, and converted to nitroso and amino derivatives. It was found that the reducing ability of nitro-BP is associated with carcinogenicity in rats: 3, 6-dinitro-BP but not 1, 6-dinitro-BP was tumorigenic in the local site by subcutaneous injection into rats. These results are important for detecting chemical mutagens/carcinogens which are emitted in completein combustion of fossile fuels.

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