Comparative tumorigenicity of 1- and 3-nitrobenzo[a]pyrenes, and 3,6- and 1,6-dinitrobenzo[a]pyrenes in F344/DuCrj rats
| Autor: | Nobuyuki Sera, Hiroshi Tokiwa, Kazumi Horikawa, Koichi Murakami, Nobuya Sano, Keisuke Izumi |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Skin Neoplasms Carcinogenicity Tests Stereochemistry Injections Subcutaneous Chemical structure Nitro compound Pharmacology Toxicology Structure-Activity Relationship Subcutaneous injection chemistry.chemical_compound Injection site Benzo(a)pyrene Animals Benzopyrenes Carcinogen chemistry.chemical_classification Chemistry Body Weight General Medicine Rats Inbred F344 Rats Toxicity Benzopyrene Carcinogens Pyrene |
| Zdroj: | Toxicology Letters. 98:51-58 |
| ISSN: | 0378-4274 |
| DOI: | 10.1016/s0378-4274(98)00106-4 |
| Popis: | 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 potent mutagens for Salmonella tester strains and we have preliminarily reported 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 the NO2-substitution in the BP structure. The chemicals were suspended in equal volumes of beeswax and tricaprylin, and rats were subcutaneously injected with single doses of 500, 1000, and 2000 microg for 1- and 3-NBP, and of 8, 40, 200, and 1000 microg for 3,6- and 1,6-DNBP, and BP as a positive control. 3,6-DNBP and BP induced tumors in a dose-dependent manner at the injection site. Rats given 1000 microg of 3,6-DNBP (2924 nmol) and BP (3968 nmol) developed subcutaneous tumors at the rate of 70 and 80%, respectively, and those given a minimum dose of 23 nmol 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 microg of 1- and 3-NBP did not develop any tumors while those given a high dose, 2000 microg, of each chemical developed tumors at only one of ten animals used. It was concluded, therefore, that these chemicals are weak carcinogens. Histologically, most of the tumors were malignant fibrous 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 tumors may involve its metabolites because of the lower mutagenicity of its reduction products, 1-nitroso-6-NBP and 1-amino-6-NBP. It is suggested, therefore, that tumorigenicities of NBPs and DNBPs differ according to the NO2-substitution on the chemical structure, which may be due to the possible nitroreduction of the chemicals. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect