Item – Theses Canada

OCLC number
57000505
Link(s) to full text
LAC copy
LAC copy
Author
Blacquiere, Dylan Paul Vincent,1980-
Title
Diallyl sulfone, a derivative of garlic, inactivates the cytochrome P450 enzyme CYP2E1 by forming N-alkylprotoporphyrin heme adducts.
Degree
M. Sc. -- Queen's University, 2003
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [2004]
Description
1 microfiche.
Notes
Includes bibliographical references.
Abstract
Diallyl sulfone (DASO2), a derivative of garlic formed by sequential oxidation of diallyl sulfide (DAS) and diallyl sulfoxide (DASO), has been shown to inhibit CYP2E1, a cytochrome P450 enzyme, in murine lung and liver. We tested the hypothesis that CYP2E1 inactivation occurs during DASO2 oxidation through covalent binding of an alkyl group to the heme moiety of CYP2E1, resulting in the formation of an 'N'-alkylprotoporphyrin adduct. Our objectives were to investigate the formation of these adducts in 'in vitro' and 'in vivo' systems to determine whether: (i) these adducts are formed in murine lung and liver, (ii) CYP2E1 is the target for heme alkylation, and (iii) these adducts are also formed in human tissues. Liver and lung microsomes from mouse and human tissues were incubated with DASO2, and examined for the formation of N -alkylprotoporphyrin adducts. Baculosomes (microsomes from baculovirus-infected insect cells transfected with rat CYP2E1 or CYP2B1 cDNA) were also incubated with DASO2 and examined for adduct formation. (Abstract shortened by UMI.)
ISBN
0612860779
9780612860773