Tumor-promoting activity and cytotoxicity of 3,4,3',4'-tetrachlorobiphenyl on N-nitrosomorpholine-induced murine liver foci

Effects of 3,4,3',4'-tetrachlorobiphenyl (TCB) on glucose-6-phosphatase (G6Pase)-altered hepatic foci of N-nitrosomorpholine (NNM)-treated B6C3F1 mice were investigated. TCB was chosen as a selective 3-methylcholanthrene-type inducer and tumor promoter. To initiate hepatocarcinogenesis, mice were treated with NNM (160 mg/l, in drinking water for 7 weeks), as in previous studies with the rat model. After a treatment-free interval of 22 weeks, TCB was administered (5 x 50 mg/kg, every 3 days), and liver foci were analysed 10 weeks after the start of TCB treatment. Unexpectedly, the number of G6Pase-negative and -positive foci per liver was markedly diminished following TCB treatment (to 32% and 57%, respectively). On the other hand, the mean volume of the remaining G6Pase-altered foci was enhanced, owing to an increase in the percentage of foci of large size (greater than 0.5 mm2). Throughout the experimental period of 39 weeks prolonged liver injury due to NNM and TCB treatment was demonstrated by histology and by elevated serum levels of glutamate-oxaloacetate transaminase. The results suggest that (in contrast to the rat system) TCB exhibited opposing effects on liver foci in the mouse model: (a) moderate tumor-promoting effects and (b) cytotoxic effects in NNM-injured liver, leading to decreased numbers of liver foci.