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Titolo:
MAIN DRUG-METABOLIZING ENZYME-SYSTEMS IN HUMAN NON-HODGKINS-LYMPHOMASSENSITIVE OR RESISTANT TO CHEMOTHERAPY
Autore:
RIBRAG V; MASSAAD L; JANOT F; MORIZET J; GOUYETTE A; CHABOT GG;
Indirizzi:
INST GUSTAVE ROUSSY,DEPT PHARMACOTOXICOL & PHARMACOGENET,INSERM,U140,PAVILLON RECH F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PHARMACOTOXICOL & PHARMACOGENET,INSERM,U140 F-94805 VILLEJUIF FRANCE
Titolo Testata:
Leukemia & lymphoma
fascicolo: 3-4, volume: 18, anno: 1995,
pagine: 303 - 310
SICI:
1042-8194(1995)18:3-4<303:MDEIHN>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Keywords:
DRUG-METABOLIZING ENZYMES; NON-HODGKINS LYMPHOMAS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
NO
Recensione:
Indirizzi per estratti:
Citazione:
V. Ribrag et al., "MAIN DRUG-METABOLIZING ENZYME-SYSTEMS IN HUMAN NON-HODGKINS-LYMPHOMASSENSITIVE OR RESISTANT TO CHEMOTHERAPY", Leukemia & lymphoma, 18(3-4), 1995, pp. 303-310

Abstract

Non-Hodgkin's lymphomas (NHL) are one of the most chemosensitive human malignancies. Complete response (CR) is often achieved, but many patients relapse and a second CR is difficult to obtain because of the development of chemoresistance. In an attempt to better understand the biology and the chemosensitivity of these lymphoid tumors, we assessed the main drug-metabolizing enzyme systems in normal lymphocytes, chemosensitive NHL and chemoresistant NHL. Cytochromes P-450(1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase and glutathione S-transferases (GST-alpha, -mu, -pi) were assayed by immunoblotting. UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, sulfatase, GST activity, and glutathione (GSH) content, were determined by spectral assays, Results showed the absence of all probed cytochromes P-450 in normal lymphocytes and NHL cells tested. GST activity was significantly lower in chemoresistant NHL compared to normal lymphocytes. GST-alpha wasnot detected in either normal lymphocytes or NHL cells. GST-pi was the predominant isoenzyme, and GST-mu was not detected in chemosensitiveNHL. GSH content was significantly lower in chemoresistant NHL compared to other lymphoid tissues tested. The conjugating enzymes UDP-glucuronosyltransferase and sulfatase were similar in either chemoresistantNHL compared to chemosensitive NHL. The activity of the hydrolytic enzyme beta-glucuronidase was lower in chemoresistant compared to chemosensitive NHL, whereas sulfatase was higher in sensitive NHL compared to normal lymphocytes. Epoxide hydrolase was not detected in either normal or NHL cells tested. In conclusion, these studies did not show anycytochrome P-450 in human lymphoid cells tested, but pointed out noteworthy differences for other enzyme systems tested. These data are of importance to further understand the mechanisms of drug resistance in human NHL.

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Documento generato il 24/11/20 alle ore 08:05:30