EFFECT OF METHIMAZOLE ON RAT RENAL CARCINOGENESIS INDUCED BY N-ETHYL-N-HYDROXYETHYLNITROSAMINE

The effect of methimazole on N-ethyl-N-hydroxyethylnitrosamine (EHEN)- induced renal lesions was investigated in a medium-term initiation/pro motion bioassay in male Wistar rats. EHEN-initiated rats underwent uni lateral nephrectomy of the left kidney and subsequent addition of the renal tumor promoters trisodium nitrilotriacetate (NTA), potassium dib asic phosphate (PDP), or hydroquinone (HQ), alone or in combination wi th methimazole, to the diet for 20 wk. The addition of methimazole red uced the severity of simple and adenomatous renal hyperplasias induced by NTA, PDP, and HQ, but had no effect on the number of renal cell tu mors that arose in EHEN + NTA groups. Methimazole also decreased the b romodeoxyuridine (BrdU) labeling indices, but had little effect on the expression of alpha(2u)-globulin in treated kidneys as compared to co ntrols. It appears that methimazole exhibits antagonistic properties t o nongenotoxic nephrotoxins, protecting against renal damage but not a gainst tumorigenesis, probably arising from genotoxic insult.