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

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

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Abstract

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.

Item Type: Article (Journal)
Additional Information: 4493/8407 (Staff fr 1/8/2003)
Uncontrolled Keywords: 6 o alkylguanine DNA alkyltransferase,animal experiment; animal tissue, histopathology
Subjects: R Medicine > RM Therapeutics. Pharmacology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Allied Health Sciences > Department of Basic Health Sciences (Until June 2011)
Depositing User: Assoc. Prof. Dr. Suzanah Abdul Rahman
Date Deposited: 26 Jun 2013 08:42
Last Modified: 26 Jun 2013 08:42
URI: http://irep.iium.edu.my/id/eprint/8407

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