COMPARATIVE TUMORIGENICITY OF 1-NITROBENZO[A]PYRENES AND 3-NITROBENZO[A]PYRENES, AND 3,6-DINITROBENZO[A]PYRENES AND 1,6-DINITROBENZO[A]PYRENES IN F344 DUCRJ RATS/

Our earlier study revealed that 1- and 3-nitrobenzo[a]pyrene (NBP), 1, 6- and 3,6-dinitrobenzo[a]pyrene (DNBP), nitrated derivatives of benzo [a]BP (BP), are present in the environment. These derivatives are pote nt mutagens for Salmonella tester strains and we have preliminarily re ported them to be carcinogenic in F344/DuCrj rats. In this study, the tumorigenic action of 1- and 3-NBP, 1,6- and 3,6-DNBP, and BP induced by subcutaneous injection into rats was found to differ according to t he NO2-substitution in the BP structure. The chemicals were suspended in equal volumes of beeswax and tricaprylin, and rats were subcutaneou sly injected with single doses of 500, 1000, and 2000 mu g for 1- and 3-NBP, and of 8, 40, 200, and 1000 mu g for 3,6- and 1,6-DNBP, and BP as a positive control. 3,6-DNBP and BP induced tumors in a dose-depend ent manner at the injection site. Rats given 1000 mu g of 3,6-DNBP (29 24 nmol) and BP (3968 nmol) developed subcutaneous tumors at the rate of 70 and 800io, respectively, and those given a minimum dose of 23 nm ol for 3,6-DNBP and 32 nmol for BP per rat developed tumors at a rate of 4.8 and 18.2%, respectively. However, rats given 500 and 1000 mu g of 1- and 3-NBP did not develop any tumors while those given a high do se, 2000 mu g, of each chemical developed tumors at only one of ten an imals used. It was concluded, therefore, that these chemicals are weak carcinogens. Histologically, most of the tumors were malignant fibrou s histiocytomas. Rats given various doses of 1,6-DNBP did not develop any tumors at the injection site. The failure of 1,6-DNBP to induce tu mors may involve its metabolites because of the lower mutagenicity of its reduction products, 1-nitroso-6-NBP and 1-amino-6-NBP. It is sugge sted, therefore, that tumorigenicities of NBPs and DNBPs differ accord ing to the NO2-substitution on the chemical structure, which may be du e to the possible nitroreduction of the chemicals. (C) 1998 Elsevier S cience Ireland Ltd. All rights reserved.