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Titolo:
PRINCIPAL DRUG-METABOLIZING ENZYME-SYSTEMS IN L1210 LEUKEMIA SENSITIVE OR RESISTANT TO BCNU IN-VIVO
Autore:
RIBRAG V; MASSAAD L; JANOT F; BISSERY MC; PARISE O; GOUYETTE A; CHABOT GG;
Indirizzi:
INST GUSTAVE ROUSSY,DEPT PHARMACOTOXICOL & PHARMACOGENET,CNRS,URA 147,PAVILLON RECH F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PHARMACOTOXICOL & PHARMACOGENET,CNRS,URA 147F-94805 VILLEJUIF FRANCE RHONE POULENC RORER SA F-94400 VITRY FRANCE
Titolo Testata:
Leukemia research
fascicolo: 11, volume: 18, anno: 1994,
pagine: 829 - 835
SICI:
0145-2126(1994)18:11<829:PDEILL>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMAS; BRAIN TUMOR-CELLS; GLUTATHIONE CONTENT; HUMAN-LIVER; S-TRANSFERASE; DOSE THERAPY; CHEMOTHERAPY; CANCER; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA;
Keywords:
DRUG-METABOLIZING ENZYMES; L1210 LEUKEMIA; BISCHLOROETHYL NITROSOUREA (BCNU) RESISTANCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
V. Ribrag et al., "PRINCIPAL DRUG-METABOLIZING ENZYME-SYSTEMS IN L1210 LEUKEMIA SENSITIVE OR RESISTANT TO BCNU IN-VIVO", Leukemia research, 18(11), 1994, pp. 829-835

Abstract

1, 3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance has been mostly studied in vitro. In an attempt to better understand BCNU resistance in the in vivo situation, we compared the principal drug-metabolizing enzyme systems in two L1210 leukemia lines, one sensitive and one resistant to BCNU (L1210/BCNU), passaged in vivo in mice. The following enzymes were assayed by immunoblotting: cytochromes P-450 (1A1/1A2, 2B1/2B2, 2C8-10, 2E1, 3A), epoxide hydrolase (EH) and glutathione S-transferases (GST-alpha, -mu and -pi). The following enzymes and cofactorswere assayed fluorometrically or spectrophotometrically: 1-chloro-2-4dinitrobenzene-GST (CDNB-GST), total glutathione (GSH), UDP-glucuronosyltransferase, beta-glucuronidase, sulfatase and sulfotransferase. Results showed that cytochrome P-450 1A1/1A2 was the only isoenzyme detected in both L1210 and L1210/BCNU. CDNB-GST activity was significantlyhigher in L1210/BCNU compared with L1210. The isoenzyme GST-alpha wasmore abundant in L1210/BCNU compared with L1210, whereas GST-pi was expressed less in the BCNU-resistant leukemia line. GST-mu was not detected in either L1210 leukemia lines. GSH levels were similar in the two L1210 lines. No significant difference was observed between the two leukemia lines for the conjugative enzymes UDP-glucuronosyltransferaseand sulfotransferase, whereas their corresponding hydrolytic enzymes beta-glucuronidase and sulfatase were about two-fold lower in the BCNU-resistant leukemia line. Epoxide hydrolase was 1.3-fold higher in L1210/BCNU compared with L1210 and this level was about three-fold higherthan in mouse liver. In conclusion, these studies showed the presenceof cytochrome P-450 1A1/1A2 in the two L1210 leukemia lines studied, and indicated noteworthy differences between the two leukemia lines for many enzyme systems such as GST, beta-glucuronidase, sulfatase and epoxide hydrolase. These data are of importance to better understand the mechanisms of drug resistance to nitrosoureas in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 08:30:39