HISTOCHEMICAL CHARACTERIZATION OF FOCAL HEPATIC-LESIONS INDUCED BY SINGLE DIETHYLNITROSAMINE TREATMENT IN INFANT MICE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (6) , 2774-2780
Abstract
Focal hepatocellular lesions, induced in an infant mouse system (15-day-old B6C3F1 mice) by a single carcinogenic dose of diethylnitrosamine (2.5 or 5.0 .mu.g/g body wt), were characterized histochemically using toluidine blue, periodic acid-Schiff, glycogen phosphorylase, glycogen synthetase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, ATPase, .gamma.-glutamyl transpeptidase and acid phosphatase. Animals were killed 5, 12, 18 and 24 wk following diethylnitrosamine treatment. The 1st focal lesions were observed in mice killed at 12 wk. All foci showed patchy cytoplasmia basophilia and a slight decrease in the glycogen content. The early foci (12 wk) showed no change in the levels of glycogen phosphorylase and glycogen synthetase, a strong reduction of glucose-6-phosphatase and a high increase in glucose-6-phosphate dehydrogenase. In addition, 56% of foci in males and 86% of foci in females showed a slight rise in glyceraldehyde-3-phosphate dehydrogenase and 12% of foci in males and 17% of foci in females had a lower acid phosphatase. The level of cytoplasmic ATPase was slightly decreased in 22% of foci. By 24 wk, a decrease in the activity of cytoplasmic ATPase was observed in 84 and 100% of foci in males and females, respectively. The increase in the membrane ATPase was observed in 65% of foci in males and 7% of foci in females. By that time, the decrease in acid phosphatase was observed in 78% of foci in males an 37% of foci in females. The .gamma.-glutamyl transpeptidase failed to show any increase in its activity, indicating that this enzyme ws not a marker of the hepatocellular lesions developing under the experimental conditions. Strong decrease in glucose-6-phosphate in association with a manifest increase in glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase activities indicated a shift from gluconeogenesis to glycolysis. Since this metabolic shift occurred concurrently with an increase in the labeling indices and focal size, it appears that these changes act in concert, representing expression of the acquired functional and replicating potential of the focal cell population.

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