Induction of DNA double strand breaks by arsenite: comparative studies with DNA breaks induced by X-rays.
Chinese hamster ovary (CHO-K1) cell line and two of its DNA double strand break (DSB) repair deficient mutant cell lines, xrs-5 (Ku80 mutant) and irs-20 (DNA-PKcs mutant), were treated with various concentrations of sodium arsenite for 2.5h, and the colony forming abilities were studied. The wild type cells showed the highest cell survival, while xrs-5 cells showed the lowest survival, and irs-20 cells had an intermediate survival. These results are very similar to the cell survival curves induced by X-rays in these three cell lines. Our data also show the dose dependent induction of DNA-DSBs in these cell lines exposed to arsenite. However, in order to obtain a similar cell survival in wild type cells, twice as many DNA-DSBs are necessary with arsenite exposure when compared with X-rays, suggesting that the types of DNA lesions leading to DSB induced by arsenite are different from those by X-rays. Based on these data, further mechanistic investigations including the involvement of DNA-DSB repair proteins are warranted in the recovery process from arsenic (As) exposure.
Okayasu
Ryuichi
R
International Space Radiation Laboratory and Environmental Toxicological Research Group, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. rokayasu@nirs.go.jp
Takahashi
Sentaro
S
Sato
Hiroshi
H
Kubota
Yoshihisa
Y
Scolavino
Staci
S
Bedford
Joel S
JS
D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects*; D016521:Electrophoresis, Gel, Pulsed-Field; D013058:Mass Spectrometry; D009153:Mutagens / Q000494:pharmacology*; D014965:X-Rays
D018053:Arsenites; D009153:Mutagens; D004247:DNA; C015001:arsenite