Tin-protoporphyrin inhibits heme oxygenase and prevents the decline in hepatic heme and cytochrome P-450 contents produced in nude mice by tumor transplantation.
Heme and hemeprotein perturbations are present in nude mice bearing transplanted tumors. Hepatic microsomal heme oxygenase activity is increased 50-100% in tumor bearing nu/nu mice when compared with normal controls. This elevation in activity of the rate-limiting enzyme of heme degradation is associated with a 50% depletion of microsomal heme and cytochrome P-45 concentrations in liver. The synthetic heme analogue, Sn-protoporphyrin, a potent inhibitor of heme oxygenase, lowers the activity of heme oxygenase in tumor bearing animals to below control levels. This effect is associated with a normalization of hepatic heme and cytochrome P-450 contents. These findings might have implications for protecting normal cells during tumor growth and chemotherapy.
Rockefeller University, New York, NY 10021.
P S
PS
Wissel
R A
RA
Galbraith
S
S
Sassa
A
A
Kappas
D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D007942:Leukemia, Experimental / Q000378:metabolism*; D008297:Male; D008665:Metalloporphyrins; D051379:Mice; D008819:Mice, Nude; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009368:Neoplasm Transplantation; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D012016:Reference Values
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; C032628:tin protoporphyrin IX; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing)