Dimethylarsinic acid induces 8-hydroxy-2'-deoxyguanosine formation in the kidney of NCI-Black-Reiter rats.
Dirnethylarsenic peroxyl radical [(CH(3))(2)AsOO] has been postulated to be responsible for DNA damage induced by dimethylarsinic acid (DMA). In an effort to elucidate the possible mechanism of tumor-inducing potential of DMA, an experiment was designed to investigate the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a specific marker of oxidative base damage in the kidney tissues of NCI-Black Reiter (NBR) rats. Animals were divided into four groups and administered the vehicle - saline, 5, 10 and 20 mg/kg body weight respectively of DMA by gavage, once a day, 5 days a week, for a period of 4 weeks. DMA induced increase of 8-OHdG levels in the kidney of the rats treated, with the highest level at the dose of 10 mg/kg body weight. Analysis of the kidney for cell proliferation employing PCNA-positive index showed greater proliferation in the tissues of treated rats. However, DMA did not have any influence on apoptosis in this regimen. Histopathological examination of the kidney selections revealed the presence of vacuolated degeneration and dilation of the proximal tubule cells in two groups (10 and 20 mg/kg body weight). This study provides evidence to substantiate the role of DMA in inducing oxidative DNA damage in the kidney.
Department of Pathology, Osaka City University Medical School, 1-4-3, Asahi-mach, Abeno-ku, 545-8585, Osaka, Japan.
M
M
Vijayaraghavan
H
H
Wanibuchi
R
R
Karim
S
S
Yamamoto
C
C
Masuda
D
D
Nakae
Y
Y
Konishi
S
S
Fukushima
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis; D002101:Cacodylic Acid / Q000633:toxicity*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis*; D006540:Herbicides / Q000633:toxicity; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats
D006540:Herbicides; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D002101:Cacodylic Acid; D003849:Deoxyguanosine