MODIFICATION OF CARCINOGENESIS BY ALPHA-TOCOPHEROL, T-BUTYLHYDROQUINONE, PROPYL GALLATE AND BUTYLATED HYDROXYTOLUENE IN A RAT MULTIORGAN CARCINOGENESIS MODEL

Effects of the dietary antioxidants alpha-tocopherol (alpha-Toc), t-bu tylhydroquinone (TBHQ), propyl gallate (PG) and butylated hydroxytolue ne (BHT) were examined using a multi-organ carcinogenesis model. Group s of 20 F344 male rats were treated with a single intragastric adminis tration of 100 mg/kg body weight N-methyl-N'-nitro-N-nitrosoguanidine, a single intragastric administration of 750 mg/kg body weight N-ethyl -N-hydroxyethylnitrosamine, two subcutaneous injections of 0.5 mg/kg b ody weight N-methylbenzyl-nitrosamine and four subcutaneous injections of 40 mg/kg body weight 1,2-dimethylhydrazine. At the same time the r ats were given 0.1% N-dibutylnitrosamine for 4 weeks and then 0.1% 2,2 '-dihydroxy-di-n-propylnitrosamine for 2 weeks in the drinking water, for a total carcinogen exposure period of 6 weeks. Starting 3 days the reafter the rats received 1% alpha-Toc, 1% TBHQ, 1% PG or 0.7% BHT in the diet, or basal diet alone. Further groups of 10-15 animals each we re treated with antioxidant alone or basal diet alone as controls. Sur viving animals were killed at the end of week 36. Histopathological ex amination showed that alpha-Toc increased the incidence of glandular s tomach atypical foci but reduced the incidence and multiplicity of kid ney atypical tubules. TBHQ significantly elevated the incidences of es ophageal papillary or nodular (PN) hyperplasias and papillomas, as wel l as forestomach papillomas, but significantly decreased the multiplic ity of colon adenocarcinomas. PG was only effective in reducing the mu ltiplicity of kidney atypical tubules. BHT enhanced the development of thyroid hyperplasias, but strongly reduced the incidence and multipli city of colon adenocarcinomas. This compound was also associated with lowered incidence and multiplicity of renal cell tumors. None of the a gents studied was unequivocal in exerting either positive or negative influence.