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. 1995 Feb 28;92(5):1332–1336. doi: 10.1073/pnas.92.5.1332

Evidence that carcinogenesis involves an imbalance between epigenetic high-frequency initiation and suppression of promotion.

K Kamiya 1, J Yasukawa-Barnes 1, J M Mitchen 1, M N Gould 1, K H Clifton 1
PMCID: PMC42513  PMID: 7877977

Abstract

Evidence is presented in support of the hypothesis that cancer development depends on an imbalance between highly frequent epigenetic initiation and suppression of promotion of the initiated cells. When irradiated clonogenic mammary epithelial cells are transplanted and hormonally stimulated, they give rise to clonal glandular structures within which carcinomas may arise. In the current study, the cancer incidence in grafts of approximately 13 7-Gy-irradiated clonogens per site indicated that at least 1 of approximately 95 clonogens was radiogenically initiated. A similar initiation frequency had been seen in grafts of approximately 5 methylnitrosourea (MNU)-treated clonogens. Such initiation is thus far more frequent than specific locus mutations. In sites grafted with larger cell inocula, cancer incidences per clonogen were suppressed inversely as the numbers of irradiated or MNU-treated clonogens per graft increased. Addition of unirradiated cells to small irradiated graft inocula also suppressed progression. Radiation and MNU thus produce quantitatively, and perhaps qualitatively, similar carcinogenesis-related sequelae in mammary clonogens.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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