title: Heme enzyme patterns in genetically and chemically induced mouse liver tumors.
abstract: Chemically induced rat hepatocyte nodules and hepatomas have repeatedly been shown to be deficient in Phase I drug-metabolizing enzymes. Some of these reduced activities are attributable to a diminution of the heme-containing terminal electron acceptor, cytochrome P-450. We recently demonstrated that spontaneous mouse liver tumors exhibit the same deficiency. Therefore, chemically induced and spontaneous liver tumors share common metabolic alterations which are likely to represent intrinsic characteristics of the tumorigenic process and are independent of its etiology. To determine whether the cytochrome P-450 deficit was the result of an altered heme metabolism, we quantitated four heme-containing proteins in normal mouse liver, spontaneous mouse liver tumors, and those induced by a single injection of diethylnitrosamine: cytochrome P-450; cytochrome b5; tryptophan 2,3-dioxygenase (EC 1.13.11.11); and catalase (EC 1.11.1.6). The amounts of these components in spontaneous tumors relative to normal liver were 0.35, 0.68, 0.76, and 0.51, respectively. Similar values were obtained with chemically induced tumors. The enzymes delta-aminolevulinic acid synthase (EC 2.3.1.37), the rate-limiting enzyme in the heme synthetic pathway, and heme oxygenase (EC 1.14.99.3), a degradative enzyme, were also quantitated. The amounts of these enzymes in spontaneous tumor relative to liver were 0.49 and 1.51, respectively. Again, similar values were observed for the chemically induced tumors. Alteration of the latter two enzyme activities may be sufficient for the altered hemoprotein patterns seen in mouse liver tumors. Further, this pattern of metabolic alteration is common to both chemically induced and spontaneous tumors. Thus, tumor resistance to cytotoxic agents activated by the monooxygenase system is not necessarily induced by exposure to these agents, nor as a result of selection.
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000032:analysis; D000818:Animals; D002374:Catalase / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005260:Female; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007501:Iron / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000032:analysis; D011990:Receptors, Transferrin; D014366:Tryptophan Oxygenase / Q000032:analysis
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D002374:Catalase; D014366:Tryptophan Oxygenase; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase