MECHANISM OF HYPEROXIA-INDUCED CHROMOSOMAL BREAKAGE IN CHINESE-HAMSTER CELLS

Exposure of cell cultures to hyperoxia, i.e., an atmosphere containing more than 20% O-2, results in various genotoxic effects. The most pro minent effect of hyperoxia is its clastogenicity. In this paper, earli er published data, obtained from research devoted to the mechanism of hyperoxia-induced clastogenesis, are reviewed. In addition, new data a re presented concerning the hyperoxia-sensitivity of the DNA-repair de ficient Chinese hamster cell lines xrs1, irs1, and EM9. None of these ionizing radiation-sensitive mutants showed hypersensitivity to hypero xia, as measured by chromosomal aberration induction and loss of clono genic cell survival. From the normal hyperoxia-sensitivity of xrs1, it may be concluded that DNA double strand breaks, of the type that are induced by ionizing radiation, do not play a role in chromosomal aberr ation formation by hyperoxia. In addition, since xrs1 is hypersensitiv e to drugs that inhibit topoisomerase II, it seems rather unlikely tha t exposure to hyperoxia affects topoisomerase II activity. Based on ci rcumstantial evidence we hypothesize that perturbation of poly(ADP-rib ose) metabolism may play a critical role in the mechanism of hyperoxia -induced clastogenesis. (C) 1993 Wiley-Liss, Inc.