Preneoplastic changes in epithelium and mesenchyme in colon of rats treated with 1,2-dimethylhydrazine

Twenty-eight rats were given weekly injections of 1,2-dimethylhydrazine (DMH) for periods of 1-10 weeks. The preneoplastic changes occurring in the descending colon were monitored by transmission electron microscopy. Marked uniformity was observed in the time period of lesion development in the colon induced by the carcinogen especially at the epithelialstromal junction in preneoplastic lesions. Little changes were observed after 3 weeks treatment with the DMH. The greatest changes occurred after 6 weeks treatment, resulting in epithelium and mesenchyme. It has been confirmed that 3 weeks treatment with DMH is subcarcinogenic, whereas 10 weeks treatment results in a high incidence of tumors. These findings are compatible with the hypothesis that a carcinogen may act by inducing alterations in a small number of enterocytes and that colonic tumors arise through stepwise evolutional changes in these cells.