Dimethylarsinic acid induces 8-hydroxy-2 '-deoxyguanosine formation in thekidney of NCI-Black-Reiter rats

Dirnethylarsenic peroxyl radical [(CH3)(2)AsOO] has been postulated to be r esponsible for DNA damage induced by dimethylarsinic acid (DMA). In an effo rt to elucidate the possible mechanism of tumor-inducing potential of DMA, an experiment was designed to investigate the formation of 8-hydroxy-2 ' -d eoxyguanosine (8 -OHdG), a specific marker of oxidative base damage in the kidney tissues of NCI-Black Reiter (NBR) rats. Animals were divided into fo ur groups and administered the vehicle saline, 5, 10 and 20 mg/kg body weig ht respectively of DMA by gavage, once a day, 5 days a week, for a period o f 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. Analys is of the kidney for cell proliferation employing PCNA-positive index showe d greater proliferation in the tissues of treated rats. However, DMA did no t have any influence on apoptosis in this regimen. Histopathological examin ation of the kidney selections revealed the presence of vacuolated degenera tion 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 D MA in inducing oxidative DNA damage in the kidney. (C) 2001 Elsevier Scienc e Ireland Ltd. All rights reserved.