Effect of hexachloro-1,3-butadiene on renal carcinogenesis in male rats pretreated with N-ethyl-N-hydroxyethylnitrosamine.

Hexachloro-1,3-butadiene (HCBD) is a potent nephrotoxicant that selectively damages the straight portion (pars recta) of the proximal tubule in the rat. To determine its effects on carcinogenesis. HCBD was administered for 30 wk at a concentration of 0.1% by weight in basal diet to male Wistar rats previously given 0.1% N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the drinking water for 2 wk. The combined treatment resulted in a significantly higher incidence of renal cell tumors than when EHEN was administered alone. This chronic exposure and a short course of a 0.2% HCBD diet for 3 wk caused marked increase in the numbers of bromodeoxyuridine-incorporating cells or proliferating cell nuclear antigen-positive cells in the outer stripe of the kidney. The ability of HCBD to promote EHEN-initiated renal tumorigenesis in rats thus appears to be associated intimately with linked nephropathy and subsequent cell proliferation.