Modification of hepato‐ and renal carcinogenesis by catechol and its isomers in rats pretreated with N‐ethyl‐N‐hydroxyethylnitrosamine

Abstract

Modifying effects of catechol, resorcinol, and hydroquinone on second stage hepato‐ and renal carcinogenesis was investigated in rats pretreated with N‐ethyl‐N‐hydroxyethyl‐nitrosamine (EHEN). Groups of twenty 6‐week‐old Wistar/Crj male rats were treated with 0.1% EHEN in the drinking water for 3 weeks. Starting 1 week after the termination of EHEN treatment, they were given a diet containing 0.8% catechol, 0.8% resorcinol, or 0.8% hydroquinone or basal diet for 36 weeks. Further groups of 15 rats were each treated with the same doses of phenolic compounds or basal diet alone without EHEN pretreatment. All surviving animals were killed at the end of week 40 when histopathological assessment revealed significant reduction of the numbers per rat of hepatocellular adenomas and hepatocellular carcinomas by resorcinol, whereas hydroquinone significantly enhanced the numbers per rat of renal microadenomas and renal cell tumors. On the other hand, the number of α_2u‐globulin positive tubules in the animals treated with hydroquinone was significantly lower than controls, without any alteration in bromodeoxyuridine (BrdU) incorporation. Lipid peroxidation, as evaluated by thiobarbituric acid reactive substance (TBARS), was at control levels in the kidneys of rats treated with hydroquinone throughout the experiment. The results showed that the known renal carcinogen hydroquinone potently enhances the second stage of EHEN‐induced renal carcinogenesis, while its isomer resorcinol inhibited hepatocarcinogenesis. α_2u‐Globulin and lipid peroxidation may not play roles in hydroquinone‐associated promotion of renal carcinogenesis. ©1993 Wiley‐Liss, Inc.