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...

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Main Authors:	Thompson, M. J., Abdul Rahman, Suzanah, Baker, T. G., Rafferty, J. A, Margison, G. P., Bibby, M. C
Format:	Article
Language:	English
Published:	Society for Reproduction and Fertility 2000
Subjects:	RM Therapeutics. Pharmacology
Online Access:	http://irep.iium.edu.my/8407/ http://irep.iium.edu.my/8407/1/J._Reprod_fertility.pdf

id	iium-8407
recordtype	eprints
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
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RM Therapeutics. Pharmacology
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
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.
format	Article
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.
title	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_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_sort	role of o6-alkylguanine-dna alkyltransferase in the resistance of mouse spermatogenic cells to o6-alkylating agents
publisher	Society for Reproduction and Fertility
publishDate	2000
url	http://irep.iium.edu.my/8407/ http://irep.iium.edu.my/8407/1/J._Reprod_fertility.pdf
first_indexed	2023-09-18T20:18:06Z
last_indexed	2023-09-18T20:18:06Z
_version_	1777407923459194880

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

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