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Titolo:
SCREENING OF MAIN DRUG-METABOLIZING-ENZYMES IN MOUSE AND HUMAN COLON TUMORS
Autore:
MASSAAD L; DEWAZIERS I; RIBRAG V; JANOT F; MORIZET J; BEAUNE PH; GOUYETTE A; CHABOT GG;
Indirizzi:
INST GUSTAVE ROUSSY,PHARMACOL CLIN LAB,CNRS,URA 147,INSERM,U140 F-94805 VILLEJUIF FRANCE CHU NECKER ENFANTS MALAD,INSERM,U75 F-75730 PARIS 15 FRANCE
Titolo Testata:
Bulletin du cancer
fascicolo: 5, volume: 80, anno: 1993,
pagine: 397 - 407
SICI:
0007-4551(1993)80:5<397:SOMDIM>2.0.ZU;2-O
Fonte:
ISI
Lingua:
FRE
Soggetto:
GLUTATHIONE-S-TRANSFERASE; HUMAN-LIVER; COLORECTAL-CARCINOMA; ANTICANCER DRUGS; HUMAN-TISSUES; CYTOCHROME-P-450; ACID; PEROXIDASE; EXPRESSION; CANCER;
Keywords:
DRUG-METABOLIZING ENZYME; HUMAN COLON TUMOR; COLON-38;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
L. Massaad et al., "SCREENING OF MAIN DRUG-METABOLIZING-ENZYMES IN MOUSE AND HUMAN COLON TUMORS", Bulletin du cancer, 80(5), 1993, pp. 397-407

Abstract

Since drug-metabolizing enzymes may influence the toxic response of tissues or organs to drugs, we studied their expression in human and colon tumor tissues, in an attempt to find new targets for chemotherapy and also to explain the intrinsic drug-insensitivity of most colon tumors to anticancer drugs. In the present work, we compared human colorectal tumors and peritumoral tissues to a mouse colorectal tumor (Co38)and normal murine colon with regard to their main drug-metabolizing enzyme systems. We investigated cytochromes P-450 (1A1/1A2, 2B1/B2, 2C,2E1, 3A) and epoxide hydrolase (EH) by immunoblotting. Total glutathione (GSH) and the activities of the following enzymes: total GST, selenium-independent glutathione peroxidase (GPX), 1,2-dichloro-4-nitrobenzene-GST(DCNB-GST), ethacrynic acid-GST(EA-GST), UDP-glucuronosyltransferase 1 (UDPGT1), beta-glucuronidase (betaG), sulfotransferase (ST) and sulfatase (S) were investigated by fluorometric and spectrophotometric assays. Results obtained by immunoblotting showed that mouse colontumor Co38 did not express any of the probed cytochromes P-450, whereas human tumors showed the presence of cytochrome P-450 3A. EH was notexpressed in either mouse colon tumor Co38 or normal mouse colon, whereas it was expressed in human peritumoral and tumoral colon tissues at similar levels. GPX and EA-GST were detected in all tumoral and non tumoral tissues of both species. DCNB-GST was expressed in all murine tissues investigated, but was not found in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzymes levels, whereas mouse colon tumor Co38 had a lower expression of DCNB-GST and EA-GST compared to normal mouse colon. No significant difference was observed between human tumors andperitumoral tissues for total GST, UDPG T1, betaG, ST and S activities. For murine colon tissues, the conjugation pathways (total GST, UDPGT1 and ST) were lower in Co38, whereas the opposite was observed for the hydrolytic enzymes (betaG and S). In conclusion, despite similarities between human and murine colon tumors, mouse colon tumor Co38 appears different from human colon tumors for many drug-metabolizing enzymesystems. These interspecies differences may have implications with regard to drug screening methodologies and preclinical evaluation of candidate anticancer drugs useful in the chemotherapy of human colorectaltumors.

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Documento generato il 02/12/20 alle ore 15:03:41