Effects of dietary retinyl acetate on the promotion of hepatic enzyme-altered foci by polybrominated biphenyls in initiated rats

Vitamin A inhibits the development of some chemically-induced tumours. Since polybrominated biphenyls (PBBs) are hepatic tumour promoters and they affect vitamin A homeostasis in rats, we put forward the hypothesis that dietary levels of vitamin A would influence tumour promotion by PBBs. In the study described here, female Sprague-Dawley rats were initiated on day 1 by ip administration of diethylnitrosamine. On day 7 after initiation, the rats were fed a vitamin A-deficient basal diet that was supplemented with either 2000 IU (low-vitamin A) or 200,000 IU (high-vitamin A) retinyl acetate/kg feed. From day 30 after initiation until the end of the study the following PBBs were added to the diets: Firemaster BP-6 (10 ppm), 2,4,5,2',4',5'-hexabromobiphenyl (10 ppm) or 3,4,5,3',4',5'-hexabromobiphenyl (1 ppm). The control animals received low- or high-vitamin A diets containing no PBBs. On day 180, the rats were necropsied, sections of various tissues were stained for histopathological examination and an evaluation of hepatic enzyme-altered foci was performed. Numbers of gamma-glutamyl transpeptidase-positive foci/cm3 liver and the mean volumes of these foci were lower in the high-vitamin A groups than those in the corresponding low-vitamin A groups, but these differences were not significant. The percentage of the liver volume occupied by foci was significantly greater in the low-vitamin A with 345-HBB group than in the corresponding high-vitamin A group. Thus, high dietary levels of vitamin A had some inhibitory effect on the promotion of hepatic-altered foci by 345-HBB in initiated rats.