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 |
| Published: |
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 |
| Summary: | 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. |
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