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

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  • Experimental Oncology
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Summary

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 (5×50 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 (>0.5mm2). 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.

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Abbreviations

G6Pase:

glucose-6-phosphatase

NNM:

N-nitrosomorpholine

TCB:

3,4,3′,4′-tetrachlorobiphenyl

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Kobusch, A.B., Fischer, G. & Bock, K.W. Tumor-promoting activity and cytotoxicity of 3,4,3′,4′-tetrachlorobiphenyl on N-nitrosomorpholine-induced murine liver foci. J Cancer Res Clin Oncol 115, 247–252 (1989). https://doi.org/10.1007/BF00391697

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