Changes in the expression of cytochrome P450 isozymes and related carcinogen metabolizing enzyme activities in Schistosoma mansoni-infected mice.

2.50
Hdl Handle:
http://hdl.handle.net/10541/84319
Title:
Changes in the expression of cytochrome P450 isozymes and related carcinogen metabolizing enzyme activities in Schistosoma mansoni-infected mice.
Authors:
Sheweita, S A; Mubark, J; Doenhofe, M J; Mostafa, M H; Margison, Geoffrey P; O'Connor, Peter J; Elder, Rhoderick H
Abstract:
Mixed-function oxidase enzymes metabolize most xenobiotic agents. Western blotting was used to investigate the effect of Schistosoma mansoni infection on the expression of various cytochrome P450 (CYP) isozymes and specific enzyme assays to study related metabolic functions in mouse liver microsomes. Male BK-TO mice were infected with 200 cercariae per mouse and their livers were assayed at 6, 15, 30 and 45 days post-infection (p.i.) and compared with appropriately matched controls. The expression of each of the CYP isozymes (1A1, 2B1/2, 2C6, and 4A) was either unaffected or transiently increased up to 30 days post-infection. By 45 days, a significant loss of signal was observed, particularly for CYP 1A1 and 2B1 /2 where no signal could be detected. Evidence supporting these findings was obtained from enzyme assays specific for particular CYP isozymes. The activity of ethoxyresorufin O-deethylase (CYP 1A1) was reduced by 97% and that of pentoxyresorufin O-depentylase (CYP 2B1 /2) by 96% at 45 days p.i. Similarly, the activity of ethoxycoumarin hydroxylase was progressively reduced over the period under study. It is believed that N-nitrosamines are activated principally by N-nitrosodimethylamine N-demethylase I which was significantly increased at both 30 and 45 days p.i. To further investigate metabolic competency following S. mansoni infection, the in vitro binding of benzo(a)pyrene metabolites to DNA was measured, using isolated liver microsomes to activate benzo(a)pyrene. Benzo(a)-pyrene-DNA adduct formation was markedly increased at 6,15 and 30 days with a maximum at 15 days, but decreased at 45 days p.i. It was concluded that S. mansoni infection changes the expression of different CYP isozymes and also the activity of phase I drug-metabolizing enzymes at different periods of infection and may thus change the liver's capacity to activate or detoxify many endogenous and exogenous compounds. Such alterations may also change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis.
Affiliation:
CRC Carcinogenese Group, Paterson Institute for Cancer Research, Christie Hopsital (NHS) Trust, Masnchester, UK. M20 4BX
Citation:
Changes in the expression of cytochrome P450 isozymes and related carcinogen metabolizing enzyme activities in Schistosoma mansoni-infected mice. 2002, 76 (1):71-8 J. Helminthol.
Journal:
Journal of Helminthology
Issue Date:
Mar-2002
URI:
http://hdl.handle.net/10541/84319
PubMed ID:
12018200
Type:
Article
Language:
en
ISSN:
0022-149X
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorSheweita, S Aen
dc.contributor.authorMubark, Jen
dc.contributor.authorDoenhofe, M Jen
dc.contributor.authorMostafa, M Hen
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorO'Connor, Peter Jen
dc.contributor.authorElder, Rhoderick Hen
dc.date.accessioned2009-10-16T11:02:42Z-
dc.date.available2009-10-16T11:02:42Z-
dc.date.issued2002-03-
dc.identifier.citationChanges in the expression of cytochrome P450 isozymes and related carcinogen metabolizing enzyme activities in Schistosoma mansoni-infected mice. 2002, 76 (1):71-8 J. Helminthol.en
dc.identifier.issn0022-149X-
dc.identifier.pmid12018200-
dc.identifier.urihttp://hdl.handle.net/10541/84319-
dc.description.abstractMixed-function oxidase enzymes metabolize most xenobiotic agents. Western blotting was used to investigate the effect of Schistosoma mansoni infection on the expression of various cytochrome P450 (CYP) isozymes and specific enzyme assays to study related metabolic functions in mouse liver microsomes. Male BK-TO mice were infected with 200 cercariae per mouse and their livers were assayed at 6, 15, 30 and 45 days post-infection (p.i.) and compared with appropriately matched controls. The expression of each of the CYP isozymes (1A1, 2B1/2, 2C6, and 4A) was either unaffected or transiently increased up to 30 days post-infection. By 45 days, a significant loss of signal was observed, particularly for CYP 1A1 and 2B1 /2 where no signal could be detected. Evidence supporting these findings was obtained from enzyme assays specific for particular CYP isozymes. The activity of ethoxyresorufin O-deethylase (CYP 1A1) was reduced by 97% and that of pentoxyresorufin O-depentylase (CYP 2B1 /2) by 96% at 45 days p.i. Similarly, the activity of ethoxycoumarin hydroxylase was progressively reduced over the period under study. It is believed that N-nitrosamines are activated principally by N-nitrosodimethylamine N-demethylase I which was significantly increased at both 30 and 45 days p.i. To further investigate metabolic competency following S. mansoni infection, the in vitro binding of benzo(a)pyrene metabolites to DNA was measured, using isolated liver microsomes to activate benzo(a)pyrene. Benzo(a)-pyrene-DNA adduct formation was markedly increased at 6,15 and 30 days with a maximum at 15 days, but decreased at 45 days p.i. It was concluded that S. mansoni infection changes the expression of different CYP isozymes and also the activity of phase I drug-metabolizing enzymes at different periods of infection and may thus change the liver's capacity to activate or detoxify many endogenous and exogenous compounds. Such alterations may also change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshBlotting, Western-
dc.subject.meshCarcinogens-
dc.subject.meshCytochrome P-450 CYP1A1-
dc.subject.meshCytochrome P-450 CYP2B1-
dc.subject.meshCytochrome P-450 Enzyme System-
dc.subject.meshIsoenzymes-
dc.subject.meshMale-
dc.subject.meshMetabolic Detoxication, Drug-
dc.subject.meshMice-
dc.subject.meshMicrosomes, Liver-
dc.subject.meshSchistosomiasis mansoni-
dc.titleChanges in the expression of cytochrome P450 isozymes and related carcinogen metabolizing enzyme activities in Schistosoma mansoni-infected mice.en
dc.typeArticleen
dc.contributor.departmentCRC Carcinogenese Group, Paterson Institute for Cancer Research, Christie Hopsital (NHS) Trust, Masnchester, UK. M20 4BXen
dc.identifier.journalJournal of Helminthologyen
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