Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents
The O6-alkylguanine-DNA alkyltransferase inactivator O6-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 O6-alkylguanine-DNA alkyltransferase in the protection of the testis against a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Society for Reproduction and Fertility
2000
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/8407/ http://irep.iium.edu.my/8407/1/J._Reprod_fertility.pdf |
| _version_ | 1848776998256640000 |
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| author | Thompson, M. J. Abdul Rahman, Suzanah Baker, T. G. Rafferty, J. A Margison, G. P. Bibby, M. C |
| author_facet | Thompson, M. J. Abdul Rahman, Suzanah Baker, T. G. Rafferty, J. A Margison, G. P. Bibby, M. C |
| author_sort | Thompson, M. J. |
| building | IIUM Repository |
| collection | Online Access |
| description | The O6-alkylguanine-DNA alkyltransferase inactivator O6-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 O6-alkylguanine-DNA
alkyltransferase in the protection of the testis against anti-cancer O6-alkylating agents.
Exposure of the mice to 1,3-bis(2-chloroethyl)-1-nitrosourea or O6-benzylguanine alone
did not produce any marked testicular toxicity at the times studied. Testicular
O6-alkylguanine-DNA alkyltransferase concentrations were assayed between 0 and
240 min after O6-benzylguanine treatment and were shown to be > 95% depleted 15 min
after treatment with O6-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 O6-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. |
| first_indexed | 2025-11-14T14:38:59Z |
| format | Article |
| id | iium-8407 |
| institution | International Islamic University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T14:38:59Z |
| publishDate | 2000 |
| publisher | Society for Reproduction and Fertility |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | iium-84072013-06-26T00:42:09Z http://irep.iium.edu.my/8407/ Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents Thompson, M. J. Abdul Rahman, Suzanah Baker, T. G. Rafferty, J. A Margison, G. P. Bibby, M. C RM Therapeutics. Pharmacology The O6-alkylguanine-DNA alkyltransferase inactivator O6-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 O6-alkylguanine-DNA alkyltransferase in the protection of the testis against anti-cancer O6-alkylating agents. Exposure of the mice to 1,3-bis(2-chloroethyl)-1-nitrosourea or O6-benzylguanine alone did not produce any marked testicular toxicity at the times studied. Testicular O6-alkylguanine-DNA alkyltransferase concentrations were assayed between 0 and 240 min after O6-benzylguanine treatment and were shown to be > 95% depleted 15 min after treatment with O6-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 O6-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. Society for Reproduction and Fertility 2000 Article PeerReviewed application/pdf en http://irep.iium.edu.my/8407/1/J._Reprod_fertility.pdf Thompson, M. J. and Abdul Rahman, Suzanah and Baker, T. G. and Rafferty, J. A and Margison, G. P. and Bibby, M. C (2000) Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents. Journal of Reproduction and Fertility, 119. pp. 339-346. ISSN 0022-4251 |
| spellingShingle | RM Therapeutics. Pharmacology Thompson, M. J. Abdul Rahman, Suzanah Baker, T. G. Rafferty, J. A Margison, G. P. Bibby, M. C Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents |
| title | Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents |
| title_full | Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents |
| title_fullStr | Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents |
| title_full_unstemmed | Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents |
| title_short | Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents |
| title_sort | role of o6-alkylguanine-dna alkyltransferase in the resistance of mouse spermatogenic cells to o6-alkylating agents |
| topic | RM Therapeutics. Pharmacology |
| url | http://irep.iium.edu.my/8407/ http://irep.iium.edu.my/8407/1/J._Reprod_fertility.pdf |