Sequential study on the synergistic effects of 2,2',4,4',5,5'-hexabromobiphenyl and 3,3',4,4',5,5'-hexabromobiphenyl on hepatic tumor promotion

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Abstract
A sequential study was completed to determine the effect of polybrominated biphenyl (PBB) congeners on the enhancement of gamma-glutamyl transpeptidase (GGT)-positive altered hepatic foci (AHF) and the development of hepatic nodules (HN) and carcinomas. Female Sprague-Dawiey rats were given a single dose of N -nitrosodiethylamine (NDEA) 24 h following a 70%partial hepatectomy. Thirty days later, rats were randomly assigned to groups and fed a basal diet or the basal diet containing 10 p.p.m. 2, 2', 4, 4', 5, 5'-hexa-bromobiphenyl (245-HBB), 0.1 p.p.m. 3, 3', 4, 4', 5, 5-hexa-bromobiphenyl (345-HBB) or 10 p.p.m. 245-HBB plus 0.1 p.p.m. 345-HBB for 140 days followed by a basal diet for up to another 310 days. Rats from each group were killed 170, 240 or 480 days after partial hepatectomy. Dietary exposure to 245-HBB and 245-HBB plus 345-HBB enhanced the development of AHF and HN whereas 345-HBB alone did not. The combination of 245-HBB and 345-HBB caused a synergistk effect on the development of AHF and HN. The number of hepatocellular carcinomas was low and evenly distributed among the groups of rats fed diets containing PBB.