Active oxygen species are involved in the induction of micronuclei by arsenite in XRS-5 cells.
The human carcinogen, arsenic, is genotoxic to mammalian cells in vitro. The mechanism is largely unknown, although the involvement of free radicals has been suggested. Since the X-ray sensitive Chinese hamster ovary cell line, XRS-5, is also sensitive to several free-radical generating agents, including H2O2, we have used this cell line to test whether the genotoxic effect of arsenite is mediated via the generation of active-oxygen species. The results indicate that the XRS-5 cells are more sensitive to arsenite in terms of cell-killing and micronucleus induction compared to the parental CHO-K1 cells. The level of arsenic uptake and release, the levels of elementary components for arsenic detoxification, glutathione and glutathione S-transferase activities in these two cell lines are very similar. The XRS-5 cells, however, were shown to have 6-fold lower catalase activity in comparison to CHO-K1 cells. Moreover, catalase could effectively reduce the frequency of arsenite-induced micronuclei. These results indicate that the low catalase activity may be an important reason why XRS-5 cells are more sensitive to the toxic effects of arsenite, and arsenite probably induces micronuclei via the overproduction of H2O2. The XRS-5 cells had a higher background level of micronuclei, and were also more sensitive to gamma-rays in terms of induction of micronuclei. Catalase, however, did not reduce the background level or the frequency of gamma-ray-induced micronuclei. Therefore, the lower catalase activity seems to bear little relation to the high background level of micronuclei and the hypersensitivity to gamma-rays in micronucleus induction in XRS-5 cells.
Wang
T S
TS
Institute of Radiation Biology, National Tsing-Hua University, Hsinchu, Taiwan, Republic of China.
Huang
H
H
D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D016466:CHO Cells; D002374:Catalase / Q000378:metabolism; D006224:Cricetinae; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D009154:Mutation / Q000187:drug effects* / Q000528:radiation effects; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity*
D018053:Arsenites; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D005982:Glutathione Transferase; D005978:Glutathione; C015001:arsenite