Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86121
Title:
Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents.
Authors:
Thompson, M J; Abdul-Rahman, S; Baker, T G; Rafferty, Joseph A; Margison, Geoffrey P; Bibby, M C
Abstract:
The O(6)-alkylguanine-DNA alkyltransferase inactivator O(6)-benzylguanine was administered to BALB/c mice either alone or before exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea to study the role of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase in the protection of the testis against anti-cancer O(6)-alkylating agents. Exposure of the mice to 1, 3-bis(2-chloroethyl)-1-nitrosourea or O(6)-benzylguanine alone did not produce any marked testicular toxicity at the times studied. Testicular O(6)-alkylguanine-DNA alkyltransferase concentrations were assayed between 0 and 240 min after O(6)-benzylguanine treatment and were shown to be > 95% depleted 15 min after treatment with O(6)-benzylguanine and remained at > 95% at all the times assayed. Histological examination, the reduction in testicular mass and the induction of spermatogenic cell apoptosis showed that this depletion significantly potentiated 1, 3-bis(2-chloroethyl)-1-nitrosourea-induced testicular damage after treatment. Major histological damage was apparent 42 days after treatment, demonstrating that the stem spermatogonia were significantly affected by the combination. These results demonstrate that O(6)-alkylguanine-DNA alkyltransferase plays a significant role in protecting the spermatogenic cells from damage caused by DNA alkylation and indicate that the observed toxicity may result from damage to stem spermatogonia.
Affiliation:
Clinical Oncology Unit, University of Bradford, Bradford BD7 1DP, UK.
Citation:
Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents. 2000, 119 (2):339-46 J. Reprod. Fertil.
Journal:
Journal of Reproduction and Fertility
Issue Date:
Jul-2000
URI:
http://hdl.handle.net/10541/86121
PubMed ID:
10864847
Type:
Article
Language:
en
ISSN:
0022-4251
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorThompson, M Jen
dc.contributor.authorAbdul-Rahman, Sen
dc.contributor.authorBaker, T Gen
dc.contributor.authorRafferty, Joseph Aen
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorBibby, M Cen
dc.date.accessioned2009-11-13T13:00:33Z-
dc.date.available2009-11-13T13:00:33Z-
dc.date.issued2000-07-
dc.identifier.citationRole of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents. 2000, 119 (2):339-46 J. Reprod. Fertil.en
dc.identifier.issn0022-4251-
dc.identifier.pmid10864847-
dc.identifier.urihttp://hdl.handle.net/10541/86121-
dc.description.abstractThe O(6)-alkylguanine-DNA alkyltransferase inactivator O(6)-benzylguanine was administered to BALB/c mice either alone or before exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea to study the role of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase in the protection of the testis against anti-cancer O(6)-alkylating agents. Exposure of the mice to 1, 3-bis(2-chloroethyl)-1-nitrosourea or O(6)-benzylguanine alone did not produce any marked testicular toxicity at the times studied. Testicular O(6)-alkylguanine-DNA alkyltransferase concentrations were assayed between 0 and 240 min after O(6)-benzylguanine treatment and were shown to be > 95% depleted 15 min after treatment with O(6)-benzylguanine and remained at > 95% at all the times assayed. Histological examination, the reduction in testicular mass and the induction of spermatogenic cell apoptosis showed that this depletion significantly potentiated 1, 3-bis(2-chloroethyl)-1-nitrosourea-induced testicular damage after treatment. Major histological damage was apparent 42 days after treatment, demonstrating that the stem spermatogonia were significantly affected by the combination. These results demonstrate that O(6)-alkylguanine-DNA alkyltransferase plays a significant role in protecting the spermatogenic cells from damage caused by DNA alkylation and indicate that the observed toxicity may result from damage to stem spermatogonia.en
dc.language.isoenen
dc.subject.meshAnalysis of Variance-
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshApoptosis-
dc.subject.meshCarmustine-
dc.subject.meshDNA Repair-
dc.subject.meshDrug Resistance-
dc.subject.meshEnzyme Inhibitors-
dc.subject.meshGuanine-
dc.subject.meshHalf-Life-
dc.subject.meshIn Situ Nick-End Labeling-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshSeminiferous Epithelium-
dc.subject.meshSpermatogonia-
dc.subject.meshTestis-
dc.subject.meshTime Factors-
dc.titleRole of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents.en
dc.typeArticleen
dc.contributor.departmentClinical Oncology Unit, University of Bradford, Bradford BD7 1DP, UK.en
dc.identifier.journalJournal of Reproduction and Fertilityen

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