Mechanisms of chromosomal aberration production. II. Aberrations induced by 5-bromodeoxyuridine and visible light.

Abstract We have allowed synchronized V79B Chinese hamster tissue culture cells to incorporate 5-bromodeoxyuridine (BUdR) during one DNA synthetic (S) period of the cell cycle and then determined chromosomal aberration yields induced by illumination of the cells with visible light during the succeeding pre- and post-DNA-synthetic (G 1 and G 2 ) phases of the cell cycle. At the level used, BUdR by itself induces no aberrations. Illumination during the G 1 phase following incorporation induces aberrations of the chromatid type, but none of the chromosome type. All types of chromatid aberrations are induced, including isochromatid deletions and exchange types. In contrast, when cells are illuminated during the immediately following G 2 phase, large numbers of achromatic lesions and chromatic deletions are seen at the first post-illumination mitosis, but no isochromatid deletions and few exchange-type aberrations occur. When G 2 -illuminated cells are examined in their second mitosis, however, chromatid aberrations of all types are again seen. These results are interpreted within the “repair” model of chromosomal aberration production by UV light presented earlier 3 . The model assumes that the vertebrate chromosome is mononeme, consisting of but a single DNA double helix during the prereplication G 1 phase. The initial lesions induced by illumination of BUdR-containing DNA are believed to be single-chain breaks, and the observation that G 1 illumination produces only chromatid-type aberrations is taken as additional evidence for the mononeme chromosome. Conversion of single-chain breaks into double chain breaks through the action of a single-strand nuclease is postulated to account for the production of chromatid deletions at the first mitosis of G 2 -illuminated cells. The action of this enzyme, plus a recombinational or post-replication repair mechanism, are postulated to account for the production of isochromatid deletions in G 1 -illuminated cells. A rapid decline in achromatic lesion frequency with increasing time between G 2 illumination and fixation of the cells is considered evidence for rapid rejoining of most of the initial chain breaks.