Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152

Alkylating agents are a group of compounds that have a cytotoxic effect due to their ability to form adducts with DNA. Cells possess the ability to repair this damage via an enzyme, O6-alkylguanine-DNA alkyltransferase (AGT). To study the effect of inhibiting this repair mechanism upon testicular cy...

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Main Authors: Thompson, Michael J., Abdul Rahman, Suzanah, Baker, Theresa G., Bibby, Michael Charles
Format: Article
Language:English
Published: Elsevier 1996
Subjects:
Online Access:http://irep.iium.edu.my/8409/1/Reprod_Tox_1996_Suzanah.pdf
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author Thompson, Michael J.
Abdul Rahman, Suzanah
Baker, Theresa G.
Bibby, Michael Charles
author_facet Thompson, Michael J.
Abdul Rahman, Suzanah
Baker, Theresa G.
Bibby, Michael Charles
author_sort Thompson, Michael J.
collection IIUM
description Alkylating agents are a group of compounds that have a cytotoxic effect due to their ability to form adducts with DNA. Cells possess the ability to repair this damage via an enzyme, O6-alkylguanine-DNA alkyltransferase (AGT). To study the effect of inhibiting this repair mechanism upon testicular cytotoxicity in BALB/c mice, the AGT inhibitor O6 benzylguanine (O6BG) was used in conjunction with the potential anticancer drug previous termB.4152next term. Paraffin sections were stained and examined using Chalkley scoring to identify the cells affected by the treatment. Using previous termB.4152next term alone the maximal effect upon the spermatogenic tissue was found to be after 32 days. The damage found was minor, with the spermatocytes and spermatids most affected. Using this time point it was found that the combined treatment produced widespread damage, with significant depletion of the majority of spermatogenic cell types. These results therefore indicate that differentiating spermatogenic cells are normally protected from previous termB.4152 induced damage by AGT, depletion of which significantly potentiates previous termB.4152 toxicity.
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spelling oai:generic.eprints.org:84092015-04-20T02:58:36Z http://irep.iium.edu.my/8409/ Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152 Thompson, Michael J. Abdul Rahman, Suzanah Baker, Theresa G. Bibby, Michael Charles RA1190 Toxicology RM Therapeutics. Pharmacology Alkylating agents are a group of compounds that have a cytotoxic effect due to their ability to form adducts with DNA. Cells possess the ability to repair this damage via an enzyme, O6-alkylguanine-DNA alkyltransferase (AGT). To study the effect of inhibiting this repair mechanism upon testicular cytotoxicity in BALB/c mice, the AGT inhibitor O6 benzylguanine (O6BG) was used in conjunction with the potential anticancer drug previous termB.4152next term. Paraffin sections were stained and examined using Chalkley scoring to identify the cells affected by the treatment. Using previous termB.4152next term alone the maximal effect upon the spermatogenic tissue was found to be after 32 days. The damage found was minor, with the spermatocytes and spermatids most affected. Using this time point it was found that the combined treatment produced widespread damage, with significant depletion of the majority of spermatogenic cell types. These results therefore indicate that differentiating spermatogenic cells are normally protected from previous termB.4152 induced damage by AGT, depletion of which significantly potentiates previous termB.4152 toxicity. Elsevier 1996 Article PeerReviewed application/pdf en http://irep.iium.edu.my/8409/1/Reprod_Tox_1996_Suzanah.pdf Thompson, Michael J. and Abdul Rahman, Suzanah and Baker, Theresa G. and Bibby, Michael Charles (1996) Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152. Reproductive Toxicology , 10 (1). pp. 71-77. ISSN 0890-6238 http://www.journals.elsevier.com/reproductive-toxicology/ DOC12372538-01
spellingShingle RA1190 Toxicology
RM Therapeutics. Pharmacology
Thompson, Michael J.
Abdul Rahman, Suzanah
Baker, Theresa G.
Bibby, Michael Charles
Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152
title Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152
title_full Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152
title_fullStr Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152
title_full_unstemmed Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152
title_short Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6 benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular combination, B.4152
title_sort potentiation of testicular cytotoxicity by the alkyltransferase inhibitor o6 benzylguanine and the 5 fluorouracil n 2 chloroethyl n nitrosourea molecular combination b 4152
topic RA1190 Toxicology
RM Therapeutics. Pharmacology
url http://irep.iium.edu.my/8409/1/Reprod_Tox_1996_Suzanah.pdf
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AT bakertheresag potentiationoftesticularcytotoxicitybythealkyltransferaseinhibitoro6benzylguanineandthe5fluorouraciln2chloroethylnnitrosoureamolecularcombinationb4152
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