Cell proliferation in the livers of male mice and rats exposed to the carcinogen P-dichlorobenzene: evidence for thresholds

Drug and Chemical Toxicology
T UmemuraG M Williams

Abstract

In a previous study, p-dichlorobenzene (pDCB), which is associated with tumorigenicity in male rat kidney and livers of mice of both genders, was found to produce acute increases in cell proliferation in those tissues. To determine whether sustained cell proliferation in the liver in susceptible species correlated with reported carcinogenic effects, we examined the effect of pDCB on cell proliferation in the livers and toxicity to the glutamine synthetase-expressing hepatocyte (GS+) subpopulation of male B6C3F1C3F1 mice and F344 rats. Mice were exposed for up to 4 weeks to 600, the maximally tolerated dose which increased liver tumors, 300 or 150 mg/kg. Rats were exposed to 300, 150 or 75 mg/kg for up to 4 weeks. In mice, the cumulative replicating fraction (CRF) in the livers of the high dose animals was significantly increased 16-fold at 1 week and 4-fold at 4 weeks. The CRF was also increased at 300 mg/kg at 1 week, but this subsided at 4 weeks. No increase was seen in the low dose group. In rats, the CRFs of the livers at 1 week were increased at 300 and 150 mg/kg, but returned to normal at 4 weeks. The size of the hepatic GS+ area was not affected in mice or in rats after 1 week of exposure, but comparable decreases were o...Continue Reading

References

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Citations

Oct 16, 2007·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Dallas B AronsonPatrick D Guiney
Mar 3, 1999·Regulatory Toxicology and Pharmacology : RTP·J A Barter, J H Sherman
Jul 26, 2000·Teratogenesis, Carcinogenesis, and Mutagenesis·V N RakitskyV S Turusov
Mar 14, 2002·Toxicologic Pathology·Gary M Williams, Michael J Iatropoulos

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