Lack of Promoting Potential of Dimethylarsinic Acid in the Kidney of Male NCI-Black Reiter Rats

Abstract

Humans encounter exposure to arsenic (As) in numerous ways. Dimethylarsinic acid (DMA), one of the major metabolites of inorganic arsenics in most mammals promotes kidney, urinary bladder, liver, and thyroid carcinogeneses in F344 rats. Dimethylarsenic peroxyl radical ((CH₃)₂ AsOO.) has been postulated to be responsible for the DNA damage induced by DMA. In a preliminary experiment conducted in our laboratory, subacute doses of DMA induced formation of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and increased proliferation indices in the renal cells of NCI-Black Reiter (NBR) rats which lack α_2u-globulin, which has been attributed to influence renal carcinogenesis. This prompted us to study the promoting effects of DMA on renal carcinogenesis in this strain of rats by employing the initiation-promotion model. Animals were divided into two groups (11 rats in each group). Group 1 was treated with N-ethyl-N-hydroxyethylnitrosamine (EHEN), at a concentration of 0.1% in the drinking water for 2 weeks followed by basal diet for 30 weeks. Group 2 was treated with EHEN with the same dosage as Group 1 for 2 weeks followed by 200 ppm DMA in the drinking water for 29 weeks. Neither atypical tubules nor renal cell tumors were induced in both groups, suggesting that absence of α_2u-globulin may contribute to the resistance to the above stimulus by this strain of rats. Since EHEN also initiated liver carcinogenesis, we analyzed the liver for glutathione S-transferase placental form (GST-P)-positive foci, which is a marker in rat liver carcinogenesis. There was no significant change between the two groups. Thus, DMA lacked the potential to promote kidney and liver carcinogeneses in male NBR rats.