Polychlorinated biphenyls as initiators in liver carcinogenesis: resistant hepatocyte model

A modified Solt-Farber protocol was established to investigate the potential initiating activity of lower chlorinated polychlorinated biphenyl (PCB) congeners in rat liver. Two different studies were conducted in male Fisher 344 rats. PCBs investigated were PCB3, PCB12, PCB38, and PCB77 in study 1 and PCB15, PCB52, PCB77, and the combination of PCB52 and PCB77 in study 2. Rats were subjected to partial hepatectomy followed by a single dose of the suspected initiating agent, diethylnitrosamine, or vehicle. Two weeks later all groups received selection treatment consisting of three daily doses of 2-acetylaminofluorene (2-AAF) and then a single dose of carbon tetrachloride, followed by three additional daily treatments of 2-AAF via gavage. Rats were killed 2 weeks after the last treatment of 2-AAF, and the number and volume of gamma-glutamyltranspeptidase (GGT)-positive foci were determined. Among the PCBs tested, PCB3, PCB15, PCB52, and PCB77 significantly increased the number of GGT-positive foci per cm(3) of liver and per liver. Only PCB3 and PCB15 increased the volume fraction of GGT-positive foci. Histopathologic analysis of hematoxylin- and eosin-stained liver sections showed that rats with significantly increased GGT-positive foci also had extensive cellular alteration. This effect was not seen in nonselection groups. We conclude that, under the conditions and time courses of these experiments, several PCBs have initiating activity in male Fischer 344 rats.