Dimethylarsenics reveal DNA damage induced by superoxide anion radicals.
We previously reported that DNA single-strand breaks (ssb) induced by exposure to dimethylarsinic acid (DMAA) were enhanced by the presence of paraquat (PQ), a superoxide anion radical 0 -(2)-producing agent, in cultured human alveolar type II (L-132) cells in vitro. In the present study, we examined the effect of sequential exposure of the cells to PQ and then DMAA under conditions causing no ssb by each alone, and observed a remarkable occurrence of ssb. The result suggests that 0 -(2) caused DNA damage, which became detectable as ssb by the treatment using DMAA. The DNA damage induced by the exposure to PQ alone was different from that by DMAA; PQ-induced damage was fully repaired after 24 h, while DMAA-induced damage was repaired only partially, and aphidicolin, an inhibitor of repair-serving DNA polymerases alpha, delta and/or epsilon, inhibited only the latter repair but not the former. These findings indicate that the DMAA treatment may be an effective tool to reveal DNA damage induced by 0 -(2), which to date has not been sufficiently clarified.
Kawaguchi
K
K
University of Shizuoka School of Pharmaceutical Sciences, Japan.
Oku
N
N
Rin
K
K
Yamanaka
K
K
Okada
S
S
D016590:Aphidicolin / Q000494:pharmacology; D002101:Cacodylic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000502:physiology; D004261:DNA Replication / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D010269:Paraquat / Q000494:pharmacology*; D013481:Superoxides / Q000494:pharmacology*
D013481:Superoxides; D016590:Aphidicolin; D002101:Cacodylic Acid; D004259:DNA-Directed DNA Polymerase; D010269:Paraquat