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Titolo:
MAIN DRUG-METABOLIZING AND CARCINOGEN-METABOLIZING ENZYME-SYSTEMS IN HUMAN NONSMALL CELL LUNG-CANCER AND PERITUMORAL TISSUES
Autore:
TOUSSAINT C; ALBIN N; MASSAAD L; GRUNENWALD D; PARISE O; MORIZET J; GOUYETTE A; CHABOT GG;
Indirizzi:
INST GUSTAVE ROUSSY,INSERM,U140,DEPT PHARMACOTOXICOL & PHARMACOGENET,PAVILLON RECH 2 F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,INSERM,U140,DEPT PHARMACOTOXICOL & PHARMACOGENET,PAVILLON RECH 2 F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,CNRS,URA 147 F-94805 VILLEJUIF FRANCE CTR MED CHIRURG PORTE CHOISY F-75013 PARIS FRANCE
Titolo Testata:
Cancer research
fascicolo: 19, volume: 53, anno: 1993,
pagine: 4608 - 4612
SICI:
0008-5472(1993)53:19<4608:MDACEI>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTATHIONE-S-TRANSFERASE; HUMAN-LIVER; SMOKING-HABITS; P-GLYCOPROTEIN; CYTOCHROME-P-450; SUSCEPTIBILITY; TUMORS; POLYMORPHISM; PURIFICATION; CHEMOTHERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
C. Toussaint et al., "MAIN DRUG-METABOLIZING AND CARCINOGEN-METABOLIZING ENZYME-SYSTEMS IN HUMAN NONSMALL CELL LUNG-CANCER AND PERITUMORAL TISSUES", Cancer research, 53(19), 1993, pp. 4608-4612

Abstract

To better understand the importance of drug-metabolizing enzymes in carcinogenesis and anticancer drug sensitivity of human non-small cell lung cancer, we studied the main drug-metabolizing enzyme systems in both lung tumors and their corresponding nontumoral lung tissues in 12 patients. The following enzymes were assayed by Western blot analysis:cytochromes P-450 (1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4); epoxide hydrolase; and glutathione S-transferase isoenzymes (GST-alpha, -mu and -pi). The activity of the following enzymes or cofactor were determined by spectrophotometric or fluorometric assays: glutathione S-transferase (GST); total glutathione; UDP-glucuronosyltransferase; beta-glucuronidase, sulfotransferase; and sulfatase. Results showed the presence of cytochrome P-450 1A1/1A2 in both tumoral and nontumoral tissues. P-450 1A1/1A2 levels were 3-fold lower in tumors compared to corresponding nontumoral tissues (P < 0.05). None of the other probed cytochromes P-450 were detected in either tumoral or nontumoral lung tissues. For the glutathione system, no significant difference between tumoral and nontumoral tissues was observed (GST activity, glutathione content, GST-alpha, -mu, and -pi). A positive linear correlation was observed betweenGST activity and GST-alpha or GST-pi. No significant difference was observed for the glucuronide and the sulfate pathways and their corresponding hydrolytic enzymes. Epoxide hydrolase was significantly decreased in tumors compared to nontumoral lung tissues (P < 0.05). In conclusion, these results showed differences between non-small cell lung tumors and nontumoral tissues for cytochrome P-450 1A1/1A2 and epoxide hydrolase. These differences between tumors and peritumoral tissues withregard to these drug-metabolizing enzymes could reflect differences occurring after malignant transformation and may play a role in drug sensitivity to anticancer drugs.

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Documento generato il 02/12/20 alle ore 15:37:19