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Induction of Colon Adenocarcinomas in CD Rats and Lung Adenomas in ICR Mice by 6-Nitrochrysene: Comparison of Carcinogenicity and Aryl Hydrocarbon Hydroxylase Induction in the Target Organs of Each Species¹

Divisions of Pathology [K. I., C. U., H. O., S. H., M. T.] and Organic Chemistry [K. F., N. M.], National Institute of Hygienic Sciences, 1-18-1 Kamiyoa, Setagayaku, Tokyo 158, Japan

Species and organ specificity of 6-nitrochrysene (6-NC)-induced carcinogenicity and the potential correlation with aryl hydrocarbon hydroxylase (AHH) induction in the target organs were investigated in both sexes of ICR mice and CD rats. Animals received total 6-NC doses of 1.4 µmol/mouse and 14.8 µmol/rat. The first i.p. injection was performed within 24 h of birth, then the animals were subjected to 3 and 5 weekly injections in the mouse and rat cases, and the survivors were sacrificed at weeks 24 and 32, respectively. Adenocarcinomas and dysplasias and/or adenomas of the colon in rats and lung adenomas in mice were observed in animals treated with 6-NC. However, no such lesions were observed in animals treated with the vehicle dimethyl sulfoxide alone.

AHH activities in the lung, colon, and liver of each animal after treatment with 6-NC or dimethyl sulfoxide were also investigated. Six-week-old animals received a single 6-NC injection i.p. at the dose of 0.8 µmol/mouse or 8.0 µmol/rat. Animals were sacrificed on day 1 or 7 following injections, when AHH levels were measured. The results indicated enzyme levels in all these organs to be elevated by 6-NC treatment, the induction rate in the mouse lung being the highest.

These results showed that 6-NC is carcinogenic for the colon of rats, as well as the lung of mice, and that it also induces AHH activity in both target and nontarget organs.

¹ Supported by Grants-in-Aid from the Ministry of Health and Welfare, Japan.

² Present address: First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan. To whom requests for reprints should be addressed.

Received 7/26/91. Accepted 12/23/91.

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