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 species.

Abstract

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 mumol/mouse and 14.8 mumol/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 mumol/mouse or 8.0 mumol/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.