Polychlorinated biphenyls hepatotoxicity

Liver cancer can also be a consequence of exposure to hepatotoxic chemicals. Natural hepatocarcinogens include fungal aflatoxins. Synthetic hepato-carcinogens include nitrosoamines, certain chlorinated hydrocarbons, polychlorinated biphenyls (PCBs), chloroform, carbon tetrachloride, dimethyl-benzanthracene, and vinyl chloride.Table 5.15 lists the chemical compounds that induce liver cancer or cirrhosis in experimental animals or... 

Ethylene inhaled at 11.5 g/m (10,000 ppm) for 4 hours was hepatotoxic in rats pretreated with the polychlorinated biphenyl Arochlor 12 54, given orally at a dose of 3 00 pmol/kg daily for 3 days to induce liver enzymes. It is not toxic without such treatment. ... 

Therefore, in spite of remarkably increased liver injury, the animals are able to overcome injury and survive the potentiated liver toxicity (Kodavanti et al. 1992 Mehendale 1990, 1991, 1992). DDT increased the sensitivity of rats to carbon tetrachloride poisoning (McLean and McLean 1966), and mice fed 100 ppm polybrominated biphenyls (PBBs) or 200 ppm polychlorinated biphenyls (RGBs) in their diet for 28 days experienced increased carbon tetrachloride hepatotoxicity (Kluwe et al. 1979). Potentiation of renal dysfunction was also found in the PBB-pretreated mice. All of these compounds are broad-spectrum MFO inducers. 

The hepatic monooxygenase system is primarily responsible for oxidation of tetrachloroethylene. Thus, compounds that stimulate or induce tetrachloroethylene metabolism could influence the toxicity associated with exposure to this chemical. Results of experiments that have investigated possible enhancement of tetrachloroethylene-induced toxicity by increasing tetrachloroethylene metabolism have been equivocal. Pretreatment of rats with ethanol (Cornish and Adefrrin 1966 Klaassen and Plaa 1966) and phenobarbital (Cornish et al. 1973 Moslen et al. 1977) failed to enhance tetrachloroethylene hepatic toxicity. Pretreatment with polychlorinated biphenyls (PCBs), on the other hand, increased urinary excretion of tetrachloroethylene metabolites in rats and enhanced tetrachloroethylene-induced hepatotoxicity (Moslen etal. 1977). 

E. S. Reynolds and M. T. Moslen, Halothane hepatotoxicity Enhancement by polychlorinated biphenyl pretreatment, Anesthesiology 47, 19-27 (1977). 

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