Effect of Griseofulvin on 5-aminolevulinate synthase and on ferrochelatase in mouse liver neoplastic nodules.
Treatment of mice with griseofulvin for 8 months induced hepatocellular nodules in the liver which persist after discontinuation of griseofulvin feeding. We investigated the porphyrogenic effect of griseofulvin on these nodules and surrounding nonneoplastic liver after renewed short-term exposure of tumor-bearing mice to this agent. Griseofulvin treatment for 4 days led to marked elevation of the activity of 5-aminolevulinate synthase in peritumoral (3.8-fold) and control (6-fold) liver. The increase in enzyme activity was much less pronounced in the nodules (1.5-fold). Ferrochelatase activity was markedly decreased under the same experimental conditions in both peritumoral and control livers (to 18 and 13.5%, respectively, of the pretreatment values), but the effect was considerably smaller in nodules (to 40% of the pretreatment value). These results may explain the lack of porphyrin accumulation in tumor tissue.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism*; D000818:Animals; D004032:Diet; D005294:Ferrochelatase / Q000378:metabolism*; D006118:Griseofulvin / Q000494:pharmacology* / Q000633:toxicity; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008190:Lyases / Q000378:metabolism*; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D011164:Porphyrias / Q000139:chemically induced; D011524:Protoporphyrins / Q000096:biosynthesis / Q000378:metabolism
D011524:Protoporphyrins; D006118:Griseofulvin; D006418:Heme; D006427:Hemin; D000624:5-Aminolevulinate Synthetase; D008190:Lyases; D005294:Ferrochelatase