Tissue specific, acute toxic effects of the carcinogen trans-4-dimethylaminostilbene.

The acute toxicity of the carcinogen trans-4-dimethylaminostilbene was studied in Wistar rats. The animals die after oral administration of 50 mg/kg (LD50) with a latency period of 11 days. Specific lesions of the stomach epithelium together with acute bone marrow incapacity and toxic effects on peripheral blood cells lead to acute anemia, which is considered to be the cause of death. Histological observations indicate that the stomach lesions develop in three phases. Firstly, necroses appear in the proliferative area predominantly in the antrum. This leads, secondly, to cystic transformation of the antrum, cardia, and Brunner's glands and further to peptic erosions and ulcerations. Thirdly, mitotic activity increases. With lethal doses, cell replacement remains incomplete. There ist a correlation between the proliferation rate of different cell types and their susceptibility; but this cannot entirely account for the tissue-specific, systemic effects of trans-4-dimethylaminostilbene. Metabolic activation is also involved, since enzyme induction with methylcholanthrene inhibits toxicity. The study disclosed a new target tissue which may now be used to investigate the mechanism of action of reactive metabolites of an aromatic amine in acute experiments. The same stomach lesions were also observed with adriamycin. With this compound, however, the intestine is also involved.