The contribution of DNA single-strand breaks to the formation of chromosome aberrations and SCEs.

Abstract

The induction of sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) with bleomycin (BLM), hydrogen peroxide (H2O2), short-wave ultraviolet (UV)-irradiation, and long-wave UV-irradiation was investigated in V79 cells with BrdUrd-substituted DNA. The application of a Neurospora endonuclease (NE) which specifically cleaves single-stranded DNA after these treatments showed that DNA single-strand breaks (SSBs) are induced by these agents. The SSBs are converted to double-strand breaks (DSBs) by NE and become visible as CAs on metaphase chromosomes. H2O2 and both types of UV-irradiation also led to an induction of CAs and SCEs, whereas BLM only induced aberrations. Cysteine (Cys) reduced the frequency of the induced SSB-dependent CAs in all treatments, but had no influence on the SCE frequencies after BLM and H2O2 treatment and had only a slight effect on the UV-induced SCEs. The results confirm the opinion that directly induced SSBs can contribute to the induction of CAs in cells with BrdUrd-substituted DNA, but that these SSBs are not efficiently converted to SCEs. The more recent conceptions regarding the mechanism of SCE are in accordance with these findings and the conclusions derived therefrom.