期刊
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
卷 48, 期 1, 页码 54-63出版社
ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
DOI: 10.1207/s15327914nc4801_8
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资金
- NATIONAL CANCER INSTITUTE [R01CA035628, P30CA036727] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES007462] Funding Source: NIH RePORTER
- NCI NIH HHS [P30-CA-36727, R01-CA-35628] Funding Source: Medline
- NIEHS NIH HHS [R01-ES-07462] Funding Source: Medline
Garlic and Cruciferae are associated with reduced risks of several human cancers, and some of their constituents are anticarcinogenic in animals. Here we studied inhibition of in vitro metabolism of the rat esophageal carcinogen methyl-n-pentylnitrosamine (MPN) by garlic-derived allyl sulfides and by Cruciferae-derived phenethyl isothiocyanate (PEITC) and sulforaphane. The test inhibitors were incubated with [H-3]-MPN, NADPH-generating system and rat esophageal microsomes (REM) or a cytochrome P450 (CYP). [3H]-MPN activation by depentylation was assayed by HPLC with radiometric determination of [H-3]-pentaldehyde 2,4-dinitrophenylhydrazone. IC50 for depentylation of 40muM MPN by rat CYP2E1 was 5-12muM for diallyl sulfide (DAS), diallyl disulfide (DADS), and PEITC and 10-20 muM for diallyl sulfone, allyl mercaptan, and diallyl trisulfide. Maximum inhibition required preincubation of rat CYP2E1 with DAS for 15 min and with DADS for 30 min. Using these preincubation times, K-i for MPN depentylation by REM, rat and human CYP2E1, and rat CYP2A3 was 0.6-1.6muM for inhibition by DAS and 1.7-70muM for inhibition by DADS. With PEITC, Ki for MPN depentylation by REM, rat CYP2E1, and rat CYP2A3 was 0.4-4.6muM. These low K-i and IC50 values may help explain how garlic and Cruciferae inhibit carcinogenesis.
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