title: Mechanism of hyperoxia-induced chromosomal breakage in Chinese hamster cells.
abstract: Exposure of cell cultures to hyperoxia, i.e., an atmosphere containing more than 20% O2, results in various genotoxic effects. The most prominent effect of hyperoxia is its clastogenicity. In this paper, earlier published data, obtained from research devoted to the mechanism of hyperoxia-induced clastogenesis, are reviewed. In addition, new data are presented concerning the hyperoxia-sensitivity of the DNA-repair deficient Chinese hamster cell lines xrs1, irs1, and EM9. None of these ionizing radiation-sensitive mutants showed hypersensitivity to hyperoxia, as measured by chromosomal aberration induction and loss of clonogenic 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 aberration formation by hyperoxia. In addition, since xrs1 is hypersensitive to drugs that inhibit topoisomerase II, it seems rather unlikely that exposure to hyperoxia affects topoisomerase II activity. Based on circumstantial evidence we hypothesize that perturbation of poly(ADP-ribose) metabolism may play a critical role in the mechanism of hyperoxia-induced clastogenesis.
authors.affiliation: Department of Human Genetics, Free University, Amsterdam, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Gille
authors.forename: C G
authors.initials: CG
authors.lastname: van Berkel
authors.forename: H
authors.initials: H
authors.lastname: Joenje
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D002869:Chromosome Aberrations / Q000235:genetics*; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; D010100:Oxygen