The effect of promoters on 1,2-dimethylhydrazine-induced colon carcinogenesis

The influence of 12-O-tetradecanoylphorbol 13-acetate (TPA) and vincristine (VCR) on the development of colon carcinoma induced by 1,2-dimethylhydrazine (DMH) has been studied by light and electron microscopy. The ability of TPA to induce the appearance of cells with a heterogeneous genotype has been investigated by cytophotometric evaluation of DNA content. The TPA-induced phenotypic alterations have been studied by quantitative histochemistry. The influence of promoters on the outcome of DMH-induced carcinogenesis has been investigated in DMH-resistant C57 Black mice. Aneuploid DNA populations were detected in hyperplasias induced by DMH or TPA; in carcinomas, the percentage of hyperdiploid cell populations was further increased. DNA aneuploidy is defined as the genetic instability of cells that can be induced by TPA treatment alone. TPA can induce dedifferentiation of hyperplastic cells, as demonstrated by quantitative histochemistry of the intestinal mucins. TPA increased the colon tumour incidence in DMH-resistant C57 Black mice. A promoter-like action of VCR could also be observed.