Alterations of hepatic delta-aminolevulinic acid synthetase, heme oxygenase, microsomal cytochrome content and drug metabolism in rats bearing ascitic tumors AH 13, AH 66 and AH 414 and a 3-methylcholanthrene induced tumor.

Abstract

Hepatic microsomal drug-metabolizing enzyme activities, cytochrome content, delta-aminolevulinic acid (ALA) synthetase and heme oxygenase activities were studied in rats bearing ascitic tumors AH 13, AH 66 and AH 414 and a primary, 3-methylcholanthrene (3-MC)-induced, tumor. Hepatic microsomal drug-metabolizing enzyme activities and cytochrome content were decreased in rats transplanted intraperitoneally with 1-2 x 10(6) cells of ascitic tumor cell lines AH 13, AH 66 and AH 414. The extent of the decrease of the microsomal cytochrome content and enzyme activities were dependent on the tumor-bearing periods after inoculation. Hepatic microsomal heme oxygenase activity was significantly increased concurrently with the decrease of microsomal drug-metabolizing enzyme activities and cytochrome content. Hepatic ALA synthetase was not changed appreciably in these tumor-bearing rats. Similar alterations of microsomal enzyme content and activities were observed in the livers of rats transplanted subcutaneously with AH 66 tumor cells and in rats bearing a primary tumor initiated by the subcutaneous injection of 3-MC. When the tumor was surgically removed from the rats bearing AH 66 subcutaneously, these hepatic microsomal parameters returned to normal levels. Microsomal drug-metabolizing enzyme activities and cytochrome content in these ascitic tumor cells were found to be at very low levels. From these results, if appears that there is an inverse relationship between the increase of microsomal heme oxygenase activity and the decrease of cytochrome P-450 and b5 as well as drug-metabolizing enzymes in the liver of tumor bearing rats.