[Resistance to anticancer drugs in relation to cytochrome P-450].
Cytochrome p-450 is a product of a multigene family, and catalyzes the activation and the detoxication of a wide variety of exogenous as well as endogenous compounds. Recent studies have the purified forms of cytochrome p-450 and provided evidence that some anticancer agents are metabolically activated by the cytochrome. In general, cancer cells express lower amounts of cytochrome p-450 as compared to normal liver cells. We recently succeeded in purifying P-450 HFLa, a form of cytochrome P-450 in human fetal livers. Examinations using antibodies to P-450 HFLa, however, showed that proteins cross-reactive with antibodies to P-450 HFLa existed in gynecologic malignancies. Development of multiple drug resistance is usually associated with a decrease in the content of cytochrome P-450, which is in contrast with glutathione S-transferase and a few other enzymes. The mechanisms responsible for such altered enzyme activity by multiple drug resistance are unclear as yet.
Kamataki
T
T
Division of Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University.
Kitada
M
M
Komori
M
M
Inaba
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism / Q000502:physiology*; D004351:Drug Resistance; D005260:Female; D005833:Genital Neoplasms, Female / Q000201:enzymology; D006801:Humans; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D000970:Antineoplastic Agents; D003577:Cytochrome P-450 Enzyme System