ENHANCEMENT OF ESOPHAGEAL CARCINOGENESIS IN MALE F344 RATS BY DIETARYPHENYLHEXYL ISOTHIOCYANATE

The purpose of this study was to evaluate the potential effects of die tary 6-phenylhexyl isothiocyanate (PHITC) on N-nitrosomethylbenzylamin e (NMBA)-induced esophageal carcinogenesis in rats. Groups of 15 male F344 rats received weekly s.c. injections of NMBA in 20% dimethylsulfo xide or the vehicle alone for 15 consecutive weeks. Two weeks prior to initiation of carcinogen or vehicle injections rats were provided wit h modified AIN-76A diet or modified AIN-76A diet containing PHITC at l evels of 0.4, 1.0 or 2.5 mu mol/g diet. Experimental controls consiste d of groups that received only the vehicle (vehicle controls), NMBA (c arcinogen controls) or PHITC at the high dose level of 2.5 mu mol/g di et. No esophageal tumors or preneoplastic lesions were detected in rat s that received the vehicle or PHITC alone. In contrast, all rats trea ted with NMBA alone or PHITC + NMBA exhibited esophageal tumors and pr eneoplastic esophageal lesions. In groups that received PHITC + NMBA t umor multiplicity was increased by 21-29% when compared with rats trea ted with NMBA alone, indicating that PHITC enhanced esophageal tumorig enesis in this model system. These results, in conjunction with our pr evious work, demonstrate that arylalkyl isothiocyanates may inhibit or enhance esophageal tumorigenesis in the NMBA-treated rat. The ability of isothiocyanates to inhibit or enhance experimental tumorigenesis m ay depend on alkyl chain length of the isothiocyanate, the animal spec ies examined and the specific carcinogen employed.