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. 2003 Oct 28;100(22):12871-6.
doi: 10.1073/pnas.2135498100. Epub 2003 Oct 17.

Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer

Michael M Vilenchik  1 , Alfred G Knudson
Affiliations

Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer

Michael M Vilenchik et al. Proc Natl Acad Sci U S A. .

Abstract

This article extends our previous quantitative analysis of the relationship between the dynamics of the primary structure of DNA and mutagenesis associated with single-strand lesions to an analysis of the production and processing of endogenous double-strand breaks (EDSBs) and to their implications for oncogenesis. We estimate that in normal human cells approximately 1% of single-strand lesions are converted to approximately 50 EDSBs per cell per cell cycle. This number is similar to that for EDSBs produced by 1.5-2.0 Gy of sparsely ionizing radiation. Although EDSBs are usually repaired with high fidelity, errors in their repair contribute significantly to the rate of cancer in humans. The doubling dose for induced DSBs is similar to doubling doses for mutation and for the induction of carcinomas by ionizing radiation. We conclude that rates of production of EDSBs and of ensuing spontaneous mitotic recombination events can account for a substantial fraction of the earliest oncogenic events in human carcinomas.

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Figures

Fig. 1.
Fig. 1.
Flow chart of the rates of production of EDSBs from SS lesions in mammalian cells under normal conditions. 1, Rate of production per S phase of cell cycle; 2, see ref. ; 3, Number in Gy equivalent of IR (= DD).
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