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 select ively damages the straight portion (pars recta) of the proximal tubule in the rat. To determine its effects on carcinogenesis, HCBD was admi nistered 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-hydroxyethylnitros amine (EHEN) in the drinking water for 2 wk. The combined treatment re sulted in a significantly higher incidence of renal cell tumors than w hen EHEN was administered alone. This chronic exposure and a short cou rse of a 0.2% HCBD diet for 3 wk caused marked increase in the numbers of bromodeoxyuridine-incorporating cells or proliferating cell nuclea r antigen-positive cells in the outer stripe of the kidney. The abilit y of HCBD to promote EHEN-initiated renal tumorigenesis in rats thus a ppears to be associated intimately with linked nephropathy and subsequ ent cell proliferation.