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Tumour promoters induce mitotic aneuploidy in yeast

Abstract

Tumour promoters, which complete the process of carcinogenesis initiated by subthreshold doses of carcinogens, can effect changes in gene regulation and cellular differentiation1,2. Whether tumour promoters also induce genotypic changes is unclear. 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumour promoter, is inactive in gene mutation assays3–5, but has been reported by some6,7, though not others8–10, to induce sister chromatid exchanges, which may be cytological indications of recombinational events11, in mammalian cells. However, TPA alone is not recombinogenic in yeast12. We now report that in a genetic system using the yeast Saccharomyces cerevisiae13–15, TPA fails to induce recombination but induces mitotic aneuploidy—a change in chromosome number which may lead to hemizygosity of recessive mutations or to phenotypic changes due to an alteration in gene balance. The ability of other agents to induce aneuploidy in this system also correlates with their tumour-promoting activity.

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Parry, J., Parry, E. & Barrett, J. Tumour promoters induce mitotic aneuploidy in yeast. Nature 294, 263–265 (1981). https://doi.org/10.1038/294263a0

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