Show simple item record

dc.contributor.authorThompson, M J
dc.contributor.authorAbdul-Rahman, S
dc.contributor.authorBaker, T G
dc.contributor.authorRafferty, Joseph A
dc.contributor.authorMargison, Geoffrey P
dc.contributor.authorBibby, M C
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.
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
html.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.


This item appears in the following Collection(s)

Show simple item record