CHANGE OF RATIO BETWEEN FERRO- AND FERRICYTOCHROME P-450 IN LIVER IS AN INDISPENSABLE FEATURE OF NDEA-INDUCED TRANSFORMATION OF HEPATOCYTES
The changes both in total and oxidized (ferri-) cytochrome P-450 contents in microsomes (MC) isolated from liver of male rats and N-nitrosodiethylamin (NDEA)-induced hepatomas were demonstrated to be of phase character correlating with hepatocarcinogenesis stages. While initial decrease in contents of total (down to 60%) and ferricytochrome P-450 (down to 64%) associated with toxification of NDEA metabolites resulted in the change of the ratio between reduced (ferro-) and ferricytochrome P-450 towards the ferri-form, the subsequent increase in the cytochrome P-450 contents upon activation of cell proliferation was characterized by a constant ratio between ferro- and ferricytochrome P-450 with a tendency of the shift towards ferro-form. Formation of tumor nodes was accompanied by decreasing content of total cytochrome (down to 83%) as well as that of the ferri-form (down to 87%) with remaining conversion of ferrocytochrome P-450 into ferri-form. In MC isolated from hepatomas (0.5–1.5 cm in diameter), the contents of total and oxidized cytochrome P-450 were found to be 74% and 68% of the control, respectively, with the ratio between ferro- and ferricytochrome P-450 being the same as at the beginning of the active cell proliferation. The results obtained are represented in the hypothetical scheme suggesting that the ratio between ferro- and ferricytochrome P-450 in liver cells to be trended in the direction of increasing content of ferro-form only during the period of the active cellular proliferation that points to the changed properties of the monooxygenase system contributing to forming a trigger mechanism of hepatocyte malignant transformation under the action of a chemical carcinogen.
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