Abstract
In order to examine the effect of 3,5-di-tert-butyl-4-hydroxytoluene (BHT) on hepatocellular population, BHT was given orally to male rats for 7 consecutive days at dose levels of 75 or 450 mg/kg/day. BHT induced hepatocellular proliferation, increase in apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 during the treatment, and hepatocellular mitoinhibition following the withdrawal. The induction of mitoinhibition, apoptosis, and TGF-β1 might be adaptive changes in response to cell proliferation; thus the homeostasis of hepatocellular population was preserved. Although both the mechanism and the biological significance of mitoinhibition observed following the withdrawal of BHT, after a 7-day treatment period, were not elucidated, its mechanism seemed to be related to the elevation of TGF-β1 immunoreactivity and its biological significance might be similar to those with non-genotoxic hepatocarcinogens in chronic treatments.
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