Tumor promoter induces sister chromatid exchanges: relevance to mechanisms of carcinogenesis.

Abstract

12-O-Tetradecanoylphorbol 13-acetate (TPA), a powerful tumor promoter, induces sister chromatid exchanges (SCE) in V79-4 Chinese hamster lung fibroblasts whereas the nonpromoting derivative 4-O-methyl-TPA does not. Inhibitors of tumor promotion, antipain, leupeptin and fluocinolone acetonide, inhibit formation of such TPA-induced SCE. TPA is a unique agent in its induction of SCE in the absence of DNA damage, chromosome aberrations, mutagenesis or significant toxicity. TPA induces several gene functions; it might also induce enzymes involved in genetic recombination. The irreversible step in tumor promotion might be the result of an aberrant mitotic segregation event leading to the expression of carcinogen/mutagen-induced recessive genetic or epigenetic chromosomal changes.