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Enzyme Alterations Associated with Mouse Liver Degeneration and Regeneration after Single Carbon Tetrachloride Feeding^*

(From the Departments of Oncology and Pathology, University of Kansas Medical School, Kansas City, Kan.)

Following a single feeding of 0.1 cc. of 40 per cent carbon tetrachloride to strain A male mice, the changes in histological characteristics and content of succinoxidase, cytochrome oxidase, liver esterase, and acid and alkaline phosphomonoesterases of the liver during the resulting degenerative and regenerative processes have been studied and evaluated. Under the conditions of this experiment the liver necrosis, as evidenced by the reduction in viable liver cell cytoplasm, starts during the first day and reaches a maximum during the second to third days after feeding carbon tetrachloride. The tissue repair as evidenced by mitotic activity started after the first day, so that the processes of liver degeneration and regeneration proceeded concomitantly.

The destruction of liver tissue was accompanied by a reduction in all the enzymes studied. Losses in succinoxidase, cytochrome oxidase, and acid phosphomonoesterase approximated the estimated proportion of liver cell cytoplasm destroyed while alkaline phosphomonoesterase showed a lesser and liver esterase a greater extent of reduction. Subsequent to maximum mitotic activity resynthesis of new enzyme occurred. Acid phosphomonoesterase and liver esterase were restored within the new liver cells prior to maximum restoration of succinoxidase and cytochrome oxidase. All enzymes investigated except cytochrome oxidase were resynthesized within comparatively short periods of time after maximum reductions in their levels were noted.

^* This investigation was aided by grants from the Atomic Energy Commission and National Cancer Institute.

Received 11/20/50.