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alpha-Hexachlorocyclohexane (alpha-HCH) or phenobarbital (PB) elicit growth and cell multiplication in rat liver. In hypophysectomized rats, alpha-HCH and PB induce an increase in liver mass, but no increase in liver DNA. Hypophysectomy without additional treatment results in a decrease of liver size and RNA, while the DNA content remains unchanged, thereby leading to a relative DNA surplus. 1/3-hepatectomy in hypophysectomized animals leads to a small increase of hepatic DNA only; after 2/3-hepatectomy 75-80% of the original liver DNA are restored. In rats with intact hypophysis losses of liver DNA are known to be restored completely. The findings suggest that the relative DNA surplus in hypophysectomized rats prevents the stimulation of DNA synthesis by weak growth stimuli such as alpha-HCH, PB, and 1/3-hepatectomy. If the relative DNA surplus is eliminated by partial hepatectomy, the inducers do produce DNA multiplication. It is concluded that the induction of liver growth and cell multiplication by alpha-HCH and PB does not require the presence of the hypophysis or one of its hormones.

A diurnal rhythm of cell proliferation exists in the liver of young rodents and in the growing liver of rats treated with α-hexachlorocyclohexane (α-HCH). The timing of the rhythm is dependent on the time of feeding but independent from the lighting regimen. This suggests that under natural circumstances the light-dark rhythm synchronizes the rhythm of hepatocyte proliferation by con­ trolling the animals' feeding habits.

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