G 2 Subpopulation in Rat Liver Induced into Mitosis by Low-Level Exposure to Carbon Tetrachloride: An Adaptive Response

Recent findings by Mehendale ( Med. Hypoth. 33, 289-299, 1990) indicate that prior exposure to chlordecone markedly enhances CCl 4-induced lethality. It was established that chlordecone suppressed the capacity of CCl 4-induced toxicity to cause an early (i.e., 6 hr after exposure) hepatocellular division which is believed to be a critical tissue response reducing subsequent CCl 4-induced hepatotoxicity. Despite the strong evidence presented by Mehendale, occurrence of such an early cellular division has been considered unlikely since most studies indicate that cellular replacement requires from 30-60 hr depending on the agent, dose, and animal species. This paper presents evidence that supports the observations of Mehendale and indicates that the early mitoses were most likely caused by the activation of hepatocytes arrested in the G 2 phase of the cell cycle that became activated by CCl 4 treatment, induced injury, or both. The concept being put forward here requires additional experimental verification and validation.