Induction of chromosomal aberrations in active oxygen-generating systems. II. A study with hydrogen peroxide-resistant cells in culture.
Cells hyper-resistant to hydrogen peroxide (H2O2) were obtained from a Chinese hamster cell line (CHL) by repeated treatments with H2O2 at stepwise increasing concentrations. A clonal line (R-8) was approximately 10 times more resistant to H2O2 than the parental cells, and retained its resistance for about 2 months in normal medium. However, with further passages after the completion of the present study, the elevated resistance gradually decreased. Although the concentration of H2O2 required to induce chromosomal aberrations in 50% of treated cells was about 10 times higher in R-8 than in the parental cells, there were no distinct differences between the cells in the induction of chromosomal aberrations by 3 alkylating agents (N-methyl-N'-nitro-N-nitrosoguanidine, N-ethyl-N-nitrosourea and mitomycin C). The catalase activity of R-8 was 10-fold in comparison with the parental cells, but no obvious differences were seen in the activities of superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase. Therefore, the elevated H2O2-resistance seemed to be associated with the enhanced catalase activity. The induction of chromosomal aberrations in two O2- generating systems--xanthine oxidase plus hypoxanthine (XO + HX), and paraquat--was compared between R-8 cells and the ordinary CHL cells. XO + HX produced chromosomal aberrations in the parental cells but not in the R-8, while paraquat induced almost the same level of aberrations in both cell lines. This finding suggests that different active oxygens are responsible for the induction of aberrations in these two O2- generating systems, i.e., H2O2 in XO + HX and O2- in paraquat.
Sawada
M
M
Division of Mutagenesis, National Institute of Hygienic Sciences, Tokyo, Japan.
Sofuni
T
T
Ishidate
M
M
D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations; D002999:Clone Cells; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D010269:Paraquat / Q000633:toxicity; D013481:Superoxides / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D013481:Superoxides; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D014969:Xanthine Oxidase; D005980:Glutathione Reductase; D010269:Paraquat