Detection of induced male germline mutation: correlations and comparisons between traditional germline mutation assays, transgenic rodent assays and expanded simple tandem repeat instability assays.

2.50
Hdl Handle:
http://hdl.handle.net/10146/65056
Title:
Detection of induced male germline mutation: correlations and comparisons between traditional germline mutation assays, transgenic rodent assays and expanded simple tandem repeat instability assays.
Authors:
Singer, Timothy M.; Lambert, Iain B.; Williams, Andrew; Douglas, George R.; Yauk, Carole L.
Abstract:
Several rodent assays are capable of monitoring germline mutation. These include traditional assays, such as the dominant lethal (DL) assay, the morphological specific locus (SL) test and the heritable translocation (HT) assay, and two assays that have been developed more recently--the expanded simple tandem repeat (ESTR) and transgenic rodent (TGR) mutation assays. In this paper, we have compiled the limited amount of experimental data that are currently available to make conclusions regarding the comparative ability of the more recently developed assays to detect germline mutations induced by chemical and radiological agents. The data suggest that ESTR and TGR assays are generally comparable with SL in detecting germline mutagenicity induced by alkylating agents and radiation, though TGR offered less sensitivity than ESTR in some cases. The DL and HT assays detect clastogenic events and are most susceptible to mutations arising in post-spermatogonial cells, and they may not provide the best comparisons with TGR and ESTR instability. The measurement of induced ESTR instability represents a relatively sensitive method of identifying agents causing germline mutation in rodents, and may also be useful for bio-monitoring exposed individuals in the human population. Any future use of the TGR and ESTR germline mutation assays in a regulatory testing context will entail more robust and extensive characterization of assay performance. This will require substantially more data, including experiments measuring multiple endpoints, a greatly expanded database of chemical agents and a focus on characterizing stage-specific activity of mutagens in these assays, preferably by sampling epididymal sperm exposed at defined pre-meiotic, meiotic and post-meiotic stages of development.
Citation:
Mutat. Res. 2006, 598 (1-2):164-193
Journal:
Mutation research
Issue Date:
25-Jun-2006
URI:
http://hdl.handle.net/10146/65056
DOI:
10.1016/j.mrfmmm.2006.01.017
PubMed ID:
16542687
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2C-4JHMT07-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=4c0d4f0f65102e1499a84bdb712817a5
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFIACATION: Animals;Animals,Genetically Modified;biomarkers of exposure & effect: method development & validation;Canada;Female;genetics;Germ-Line Mutation;Male;Mice;Models,Genetic;Mutagenesis;Rodentia;Spermatogenesis;Tandem Repeat Sequences;Toxicology;Translocation,Genetic.
ISSN:
0027-5107
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorSinger, Timothy M.-
dc.contributor.authorLambert, Iain B.-
dc.contributor.authorWilliams, Andrew-
dc.contributor.authorDouglas, George R.-
dc.contributor.authorYauk, Carole L.-
dc.date.accessioned2009-04-16T12:20:44Z-
dc.date.available2009-04-16T12:20:44Z-
dc.date.issued2006-06-25-
dc.identifier.citationMutat. Res. 2006, 598 (1-2):164-193en
dc.identifier.issn0027-5107-
dc.identifier.pmid16542687-
dc.identifier.doi10.1016/j.mrfmmm.2006.01.017-
dc.identifier.urihttp://hdl.handle.net/10146/65056-
dc.descriptionKEYWORDS CLASSIFIACATION: Animals;Animals,Genetically Modified;biomarkers of exposure & effect: method development & validation;Canada;Female;genetics;Germ-Line Mutation;Male;Mice;Models,Genetic;Mutagenesis;Rodentia;Spermatogenesis;Tandem Repeat Sequences;Toxicology;Translocation,Genetic.en
dc.description.abstractSeveral rodent assays are capable of monitoring germline mutation. These include traditional assays, such as the dominant lethal (DL) assay, the morphological specific locus (SL) test and the heritable translocation (HT) assay, and two assays that have been developed more recently--the expanded simple tandem repeat (ESTR) and transgenic rodent (TGR) mutation assays. In this paper, we have compiled the limited amount of experimental data that are currently available to make conclusions regarding the comparative ability of the more recently developed assays to detect germline mutations induced by chemical and radiological agents. The data suggest that ESTR and TGR assays are generally comparable with SL in detecting germline mutagenicity induced by alkylating agents and radiation, though TGR offered less sensitivity than ESTR in some cases. The DL and HT assays detect clastogenic events and are most susceptible to mutations arising in post-spermatogonial cells, and they may not provide the best comparisons with TGR and ESTR instability. The measurement of induced ESTR instability represents a relatively sensitive method of identifying agents causing germline mutation in rodents, and may also be useful for bio-monitoring exposed individuals in the human population. Any future use of the TGR and ESTR germline mutation assays in a regulatory testing context will entail more robust and extensive characterization of assay performance. This will require substantially more data, including experiments measuring multiple endpoints, a greatly expanded database of chemical agents and a focus on characterizing stage-specific activity of mutagens in these assays, preferably by sampling epididymal sperm exposed at defined pre-meiotic, meiotic and post-meiotic stages of development.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2C-4JHMT07-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=4c0d4f0f65102e1499a84bdb712817a5en
dc.subjectExpanded simple tandem repeaten
dc.subjectInduced mutationen
dc.subjectTransgenic rodenten
dc.subjectGermline mutationen
dc.subjectHeritable translocationen
dc.subjectSpecific locus testen
dc.subjectDominant lethal assayen
dc.subjectSpermen
dc.subject.meshAnimals-
dc.subject.meshAnimals, Genetically Modified-
dc.subject.meshFemale-
dc.subject.meshGerm-Line Mutation-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshModels, Genetic-
dc.subject.meshRodentia-
dc.subject.meshSpermatogenesis-
dc.subject.meshTandem Repeat Sequences-
dc.subject.meshTranslocation, Genetic-
dc.titleDetection of induced male germline mutation: correlations and comparisons between traditional germline mutation assays, transgenic rodent assays and expanded simple tandem repeat instability assays.en
dc.typeArticleen
dc.identifier.journalMutation researchen
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