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Titolo:
MAIN DRUG-METABOLIZING ENZYME-SYSTEMS IN HUMAN BREAST-TUMORS AND PERITUMORAL TISSUES
Autore:
ALBIN N; MASSAAD L; TOUSSAINT C; MATHIEU MC; MORIZET J; PARISE O; GOUYETTE A; CHABOT GG;
Indirizzi:
INST GUSTAVE ROUSSY,DEPT PHARMACOTOXICOL & PHARMACOGENET,PAVILLON RECH 2 F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PHARMACOTOXICOL & PHARMACOGENET,PAVILLON RECH 2 F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT ANATOMOPATHOL F-94805 VILLEJUIF FRANCE
Titolo Testata:
Cancer research
fascicolo: 15, volume: 53, anno: 1993,
pagine: 3541 - 3546
SICI:
0008-5472(1993)53:15<3541:MDEIHB>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTATHIONE-S-TRANSFERASE; HUMAN-LIVER; MULTIDRUG RESISTANCE; CANCER-CELLS; PURIFICATION; CHEMOTHERAPY; EXPRESSION; MICROSOMES; PEROXIDASE; REDUCTASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
N. Albin et al., "MAIN DRUG-METABOLIZING ENZYME-SYSTEMS IN HUMAN BREAST-TUMORS AND PERITUMORAL TISSUES", Cancer research, 53(15), 1993, pp. 3541-3546

Abstract

In an attempt to better understand breast tumors sensitivity or resistance to anticancer drugs, the main drug-metabolizing enzyme systems There evaluated in both breast tumors and their corresponding peritumoral tissues in 12 patients. The following enzymes were assayed by Western blot: cytochromes P-450 (1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4); glutathione S-transferases (GST-alpha, -mu, and -pi); and epoxide hydrolase. The activity of the following enzymes or cofactor were determined by spectrophotometric or fluorometric assays: GST; total glutathione; UDP-glucuronosyltransferase; Beta-glucuronidase; sulfotransferase; and sulfatase. Results showed the absence of all probed cytochromes P-450 in both tumoral and peritumoral tissues. GST activity was significantly (P < 0.05) higher in tumors (mean +/- SD, 399 +/- 362 nmol/min/mg) thanin corresponding peritumoral tissues (86 +/- 67). The GST isoenzymes GST-mu and GST-pi (determined by immunoblotting) were also higher in tumors than in corresponding peritumoral tissues (3- and 5-fold, respectively). Both GST-mu and GST-pi levels were significantly correlated with GST activity. GST-alpha was not detected in either tumoral or peritumoral tissues. Glutathione levels in tumors (22 +/- 23 nmol/mg protein) were not statistically different from peritumoral tissues (11 +/- 12). Epoxide hydrolase was expressed at similar levels in tumors and peritumoral tissues. The glucuronide-forming enzyme UDP-glucuronosyltransferase was 5-fold lower in tumors (0.1 +/- 0.2 nmol/h/mg) than in peritumoral tissues (0.5 +/- 1), whereas the opposite was observed for the hydrolytic enzyme beta-glucuronidase, which was 6-fold higher in tumors (736 +/- 1392 nmol/h/mg) compared to peritumoral tissues (125 +/-75). No difference was noted between tumoral and peritumoral tissues for sulfotransferase (1 +/- 2 nmol/mg), but the corresponding hydrolytic enzyme (sulfatase) was 2-fold higher in tumoral tissues (14 +/- 15 nmol/h/mg) than in peritumoral tissues (6 +/-2). In conclusion, several differences were observed between human breast tumors and peritumoral tissues for many conjugating enzymes (GST-mu, GST-pi, and UDP-glucuronosyltransferase) and hydrolytic enzymes (sulfatase and beta-glucuronidase). These noteworthy differences between tumoral and peritumoral tissues with regard to their main drug-metabolizing enzymes could play a role in the relative drug sensitivity or insensitivity of human breast cancer tissues to chemotherapeutic agents and could be potential targets for chemotherapeutic interventions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 07:52:04