Effects of Schistosoma haematobium infection on drug-metabolizing enzymes in human bladder cancer tissues.

2.50
Hdl Handle:
http://hdl.handle.net/10541/78175
Title:
Effects of Schistosoma haematobium infection on drug-metabolizing enzymes in human bladder cancer tissues.
Authors:
Sheweita, S A; El-Shahat, F G; Bazeed, M A; Abu El-Maati, M R; O'Connor, Peter J
Abstract:
The mixed function oxidase system includes the phase I drug oxidation proteins e.g. aryl hydrocarbon hydroxylase (AHH), N-nitrosodimethylamine-N-demethylase I (NDMA-dI) and cytochrome b5 which metabolize most carcinogens and xenobiotics into less and/or more active intermediates. These were determined in human bladder tissues diagnosed as bladder cancer only (10 samples) and bladder cancer associated with Schistosoma haematobium (12 samples) and normal bladder tissues (12 samples). In addition to the above enzymes, agents involved in Phase II drug metabolism e.g. glutathione and glutathione S-transferase as well as free radicals (detected as thiobarbituric acid-reactive substances, TBARS) were also determined in these tissues samples. AAH and NDMA-dI, cytochrome b5, and glutathione S-transferase activity decreased by 42, 28, 47 and 32%, respectively, in human bladder cancer tissues. In bladder cancer tissues associated with S. haematobium infection NDMA-dI and GST activity decreased further by 65 and 56%, respectively, whereas AHH activity increased by 50% and levels of reduced glutathione also increased by 43% in cancer tissue and by 29% in schistocome infected bladder cancer tissue. The level of free radicals also increased significantly (by 57%) in infected bladder cancer tissue but not at all in non-infected cancer tissue. Alterations in the activity of phase I and II of drug-metabolizing enzymes in human bladder tissues as a result of S. haematobium infection may therefore change the bladder's capacity to detoxify many endogenous compounds and may also potentiate the deleterious effects of bladder carcinogens, (e.g. N-nitrosamines) which are known to be present in relatively large quantities in the bladder of patients with schistosomiasis. The present study thus provides new insights into mechanisms for the genesis of bladder cancer initiated in association with schistosomiasis.
Affiliation:
Department of Bioscience and Technology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt. sheweita@hotmail.com
Citation:
Effects of Schistosoma haematobium infection on drug-metabolizing enzymes in human bladder cancer tissues. 2004, 205 (1):15-21 Cancer Lett.
Journal:
Cancer Letters
Issue Date:
8-Mar-2004
URI:
http://hdl.handle.net/10541/78175
DOI:
10.1016/j.canlet.2003.09.023
PubMed ID:
15036656
Type:
Article
Language:
en
ISSN:
0304-3835
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorSheweita, S A-
dc.contributor.authorEl-Shahat, F G-
dc.contributor.authorBazeed, M A-
dc.contributor.authorAbu El-Maati, M R-
dc.contributor.authorO'Connor, Peter J-
dc.date.accessioned2009-08-21T11:26:27Z-
dc.date.available2009-08-21T11:26:27Z-
dc.date.issued2004-03-08-
dc.identifier.citationEffects of Schistosoma haematobium infection on drug-metabolizing enzymes in human bladder cancer tissues. 2004, 205 (1):15-21 Cancer Lett.en
dc.identifier.issn0304-3835-
dc.identifier.pmid15036656-
dc.identifier.doi10.1016/j.canlet.2003.09.023-
dc.identifier.urihttp://hdl.handle.net/10541/78175-
dc.description.abstractThe mixed function oxidase system includes the phase I drug oxidation proteins e.g. aryl hydrocarbon hydroxylase (AHH), N-nitrosodimethylamine-N-demethylase I (NDMA-dI) and cytochrome b5 which metabolize most carcinogens and xenobiotics into less and/or more active intermediates. These were determined in human bladder tissues diagnosed as bladder cancer only (10 samples) and bladder cancer associated with Schistosoma haematobium (12 samples) and normal bladder tissues (12 samples). In addition to the above enzymes, agents involved in Phase II drug metabolism e.g. glutathione and glutathione S-transferase as well as free radicals (detected as thiobarbituric acid-reactive substances, TBARS) were also determined in these tissues samples. AAH and NDMA-dI, cytochrome b5, and glutathione S-transferase activity decreased by 42, 28, 47 and 32%, respectively, in human bladder cancer tissues. In bladder cancer tissues associated with S. haematobium infection NDMA-dI and GST activity decreased further by 65 and 56%, respectively, whereas AHH activity increased by 50% and levels of reduced glutathione also increased by 43% in cancer tissue and by 29% in schistocome infected bladder cancer tissue. The level of free radicals also increased significantly (by 57%) in infected bladder cancer tissue but not at all in non-infected cancer tissue. Alterations in the activity of phase I and II of drug-metabolizing enzymes in human bladder tissues as a result of S. haematobium infection may therefore change the bladder's capacity to detoxify many endogenous compounds and may also potentiate the deleterious effects of bladder carcinogens, (e.g. N-nitrosamines) which are known to be present in relatively large quantities in the bladder of patients with schistosomiasis. The present study thus provides new insights into mechanisms for the genesis of bladder cancer initiated in association with schistosomiasis.en
dc.language.isoenen
dc.subjectUrinary Bladder Canceren
dc.subject.meshAdult-
dc.subject.meshAnimals-
dc.subject.meshHumans-
dc.subject.meshMiddle Aged-
dc.subject.meshMixed Function Oxygenases-
dc.subject.meshSchistosomiasis haematobia-
dc.subject.meshUrinary Bladder Neoplasms-
dc.titleEffects of Schistosoma haematobium infection on drug-metabolizing enzymes in human bladder cancer tissues.en
dc.typeArticleen
dc.contributor.departmentDepartment of Bioscience and Technology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt. sheweita@hotmail.comen
dc.identifier.journalCancer Lettersen
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