Dose--Response Curve for Ethylnitrosourea-Induced Specific-Locus Mutations in Mouse Spermatogonia
The extreme mutagenic effectiveness of N-ethyl-N-nitrosourea in the mouse has permitted the accumulation of the most extensive dose--response data yet obtained for chemical induction of specific-locus mutations in spermatogonia. In the lower portion of the curve, below a dose of 100 mg/kg, the data...
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Veröffentlicht in: | Proc. Natl. Acad. Sci. U.S.A.; (United States) 1982-06, Vol.79 (11), p.3589-3591 |
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creator | Russell, W. L. Hunsicker, P. R. Raymer, G. D. Steele, M. H. Stelzner, K. F. Thompson, H. M. |
description | The extreme mutagenic effectiveness of N-ethyl-N-nitrosourea in the mouse has permitted the accumulation of the most extensive dose--response data yet obtained for chemical induction of specific-locus mutations in spermatogonia. In the lower portion of the curve, below a dose of 100 mg/kg, the data fall statistically significantly below a maximum likelihood fit to a straight line. Independent evidence indicates that, over this dose range, ethylnitrosourea reaches the testis in amounts directly proportional to the injected dose. It is concluded that, despite the mutagenic effectiveness of ethylnitrosourea, the spermatogonia are apparently capable of repairing at least a major part of the mutational damage when the repair process is not swamped by a high dose. This finding is important both in basic studies on the mutagenic action of chemicals in mammals and in risk estimation. |
doi_str_mv | 10.1073/pnas.79.11.3589 |
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L. ; Hunsicker, P. R. ; Raymer, G. D. ; Steele, M. H. ; Stelzner, K. F. ; Thompson, H. M.</creator><creatorcontrib>Russell, W. L. ; Hunsicker, P. R. ; Raymer, G. D. ; Steele, M. H. ; Stelzner, K. F. ; Thompson, H. M. ; Oak Ridge National Lab., TN</creatorcontrib><description>The extreme mutagenic effectiveness of N-ethyl-N-nitrosourea in the mouse has permitted the accumulation of the most extensive dose--response data yet obtained for chemical induction of specific-locus mutations in spermatogonia. In the lower portion of the curve, below a dose of 100 mg/kg, the data fall statistically significantly below a maximum likelihood fit to a straight line. Independent evidence indicates that, over this dose range, ethylnitrosourea reaches the testis in amounts directly proportional to the injected dose. It is concluded that, despite the mutagenic effectiveness of ethylnitrosourea, the spermatogonia are apparently capable of repairing at least a major part of the mutational damage when the repair process is not swamped by a high dose. This finding is important both in basic studies on the mutagenic action of chemicals in mammals and in risk estimation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.79.11.3589</identifier><identifier>PMID: 6954505</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>550400 - Genetics ; 560305 - Chemicals Metabolism & Toxicology- Vertebrates- (-1987) ; Alleles ; Allelism ; ANIMALS ; BASIC BIOLOGICAL SCIENCES ; BIOLOGICAL EFFECTS ; BIOLOGICAL RECOVERY ; BIOLOGICAL REPAIR ; Confidence limits ; DATA ; DNA Repair ; Dose response relationship ; Dose-Response Relationship, Drug ; DOSE-RESPONSE RELATIONSHIPS ; Ethylnitrosourea - pharmacology ; EXPERIMENTAL DATA ; GAMETES ; GENE MUTATIONS ; Genetic loci ; Genetic mutation ; GERM CELLS ; INFORMATION ; Male ; MAMMALS ; MICE ; MUTAGENESIS ; Mutation - drug effects ; MUTATION FREQUENCY ; MUTATIONS ; NITROSO COMPOUNDS ; Nitrosourea Compounds - pharmacology ; NUMERICAL DATA ; ORGANIC COMPOUNDS ; ORGANIC NITROGEN COMPOUNDS ; Radiation dosage ; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT ; RECOVERY ; REPAIR ; RISK ASSESSMENT ; RODENTS ; SPERMATOGONIA ; Spermatogonia - drug effects ; Spermatozoa - drug effects ; Statistical significance ; Testes ; VERTEBRATES</subject><ispartof>Proc. Natl. Acad. Sci. 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L.</creatorcontrib><creatorcontrib>Hunsicker, P. R.</creatorcontrib><creatorcontrib>Raymer, G. D.</creatorcontrib><creatorcontrib>Steele, M. H.</creatorcontrib><creatorcontrib>Stelzner, K. F.</creatorcontrib><creatorcontrib>Thompson, H. M.</creatorcontrib><creatorcontrib>Oak Ridge National Lab., TN</creatorcontrib><title>Dose--Response Curve for Ethylnitrosourea-Induced Specific-Locus Mutations in Mouse Spermatogonia</title><title>Proc. Natl. Acad. Sci. U.S.A.; (United States)</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The extreme mutagenic effectiveness of N-ethyl-N-nitrosourea in the mouse has permitted the accumulation of the most extensive dose--response data yet obtained for chemical induction of specific-locus mutations in spermatogonia. In the lower portion of the curve, below a dose of 100 mg/kg, the data fall statistically significantly below a maximum likelihood fit to a straight line. Independent evidence indicates that, over this dose range, ethylnitrosourea reaches the testis in amounts directly proportional to the injected dose. It is concluded that, despite the mutagenic effectiveness of ethylnitrosourea, the spermatogonia are apparently capable of repairing at least a major part of the mutational damage when the repair process is not swamped by a high dose. This finding is important both in basic studies on the mutagenic action of chemicals in mammals and in risk estimation.</description><subject>550400 - Genetics</subject><subject>560305 - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)</subject><subject>Alleles</subject><subject>Allelism</subject><subject>ANIMALS</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>BIOLOGICAL EFFECTS</subject><subject>BIOLOGICAL RECOVERY</subject><subject>BIOLOGICAL REPAIR</subject><subject>Confidence limits</subject><subject>DATA</subject><subject>DNA Repair</subject><subject>Dose response relationship</subject><subject>Dose-Response Relationship, Drug</subject><subject>DOSE-RESPONSE RELATIONSHIPS</subject><subject>Ethylnitrosourea - pharmacology</subject><subject>EXPERIMENTAL DATA</subject><subject>GAMETES</subject><subject>GENE MUTATIONS</subject><subject>Genetic loci</subject><subject>Genetic mutation</subject><subject>GERM CELLS</subject><subject>INFORMATION</subject><subject>Male</subject><subject>MAMMALS</subject><subject>MICE</subject><subject>MUTAGENESIS</subject><subject>Mutation - drug effects</subject><subject>MUTATION FREQUENCY</subject><subject>MUTATIONS</subject><subject>NITROSO COMPOUNDS</subject><subject>Nitrosourea Compounds - pharmacology</subject><subject>NUMERICAL DATA</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANIC NITROGEN COMPOUNDS</subject><subject>Radiation dosage</subject><subject>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</subject><subject>RECOVERY</subject><subject>REPAIR</subject><subject>RISK ASSESSMENT</subject><subject>RODENTS</subject><subject>SPERMATOGONIA</subject><subject>Spermatogonia - drug effects</subject><subject>Spermatozoa - drug effects</subject><subject>Statistical significance</subject><subject>Testes</subject><subject>VERTEBRATES</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1982</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9vFCEUx4nR1LV6NjHRTDzU02xhGBg4eGjW1jbZxsQfZ0KZR5dmFkZgmva_l8mu1V56gvD9fN97vC9CbwleEtzR49HrtOzkkpAlZUI-QwuCJal5K_FztMC46WrRNu1L9CqlG4yxZAIfoAMuWcswWyD9JSSo6--QxuATVKsp3kJlQ6xO8-Z-8C7HkMIUQdcXvp8M9NWPEYyzztTrYKZUXU5ZZ1fMlfPVZZhKkULErc7hOninX6MXVg8J3uzPQ_Tr7PTn6rxef_t6sTpZ14YJlmtNeyI7emW4BmC8xwK4Ja3QnNJWt5ZDucpOM8yxFaQ89EIIq6koJlKoQ_R5V3ecrrbQG_A56kGN0W11vFdBO_VY8W6jrsOtoi1veVf8H3f-kLJTybgMZmOC92Cy4pRLQmboaN8kht8TpKy2LhkYBu2hfF0RVrbaNKKAxzvQlP2lCPZhEILVnJyak1OdVISoObnieP___A_8Pqqif9jrs_Gv-qjApycBZadhyHCXC_luR96kHOK_yRraSPoH6663tA</recordid><startdate>19820601</startdate><enddate>19820601</enddate><creator>Russell, W. L.</creator><creator>Hunsicker, P. R.</creator><creator>Raymer, G. D.</creator><creator>Steele, M. H.</creator><creator>Stelzner, K. F.</creator><creator>Thompson, H. M.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>19820601</creationdate><title>Dose--Response Curve for Ethylnitrosourea-Induced Specific-Locus Mutations in Mouse Spermatogonia</title><author>Russell, W. L. ; Hunsicker, P. R. ; Raymer, G. D. ; Steele, M. H. ; Stelzner, K. F. ; Thompson, H. M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-a3d1973bc6aee56d08e6f148a6334a4f6e8a697a5060f814f6d888fa3873b1a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1982</creationdate><topic>550400 - Genetics</topic><topic>560305 - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)</topic><topic>Alleles</topic><topic>Allelism</topic><topic>ANIMALS</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>BIOLOGICAL EFFECTS</topic><topic>BIOLOGICAL RECOVERY</topic><topic>BIOLOGICAL REPAIR</topic><topic>Confidence limits</topic><topic>DATA</topic><topic>DNA Repair</topic><topic>Dose response relationship</topic><topic>Dose-Response Relationship, Drug</topic><topic>DOSE-RESPONSE RELATIONSHIPS</topic><topic>Ethylnitrosourea - pharmacology</topic><topic>EXPERIMENTAL DATA</topic><topic>GAMETES</topic><topic>GENE MUTATIONS</topic><topic>Genetic loci</topic><topic>Genetic mutation</topic><topic>GERM CELLS</topic><topic>INFORMATION</topic><topic>Male</topic><topic>MAMMALS</topic><topic>MICE</topic><topic>MUTAGENESIS</topic><topic>Mutation - drug effects</topic><topic>MUTATION FREQUENCY</topic><topic>MUTATIONS</topic><topic>NITROSO COMPOUNDS</topic><topic>Nitrosourea Compounds - pharmacology</topic><topic>NUMERICAL DATA</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANIC NITROGEN COMPOUNDS</topic><topic>Radiation dosage</topic><topic>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</topic><topic>RECOVERY</topic><topic>REPAIR</topic><topic>RISK ASSESSMENT</topic><topic>RODENTS</topic><topic>SPERMATOGONIA</topic><topic>Spermatogonia - drug effects</topic><topic>Spermatozoa - drug effects</topic><topic>Statistical significance</topic><topic>Testes</topic><topic>VERTEBRATES</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Russell, W. L.</creatorcontrib><creatorcontrib>Hunsicker, P. R.</creatorcontrib><creatorcontrib>Raymer, G. D.</creatorcontrib><creatorcontrib>Steele, M. H.</creatorcontrib><creatorcontrib>Stelzner, K. F.</creatorcontrib><creatorcontrib>Thompson, H. M.</creatorcontrib><creatorcontrib>Oak Ridge National Lab., TN</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proc. Natl. Acad. Sci. U.S.A.; (United States)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Russell, W. L.</au><au>Hunsicker, P. R.</au><au>Raymer, G. D.</au><au>Steele, M. H.</au><au>Stelzner, K. F.</au><au>Thompson, H. M.</au><aucorp>Oak Ridge National Lab., TN</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dose--Response Curve for Ethylnitrosourea-Induced Specific-Locus Mutations in Mouse Spermatogonia</atitle><jtitle>Proc. Natl. Acad. Sci. U.S.A.; (United States)</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1982-06-01</date><risdate>1982</risdate><volume>79</volume><issue>11</issue><spage>3589</spage><epage>3591</epage><pages>3589-3591</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The extreme mutagenic effectiveness of N-ethyl-N-nitrosourea in the mouse has permitted the accumulation of the most extensive dose--response data yet obtained for chemical induction of specific-locus mutations in spermatogonia. In the lower portion of the curve, below a dose of 100 mg/kg, the data fall statistically significantly below a maximum likelihood fit to a straight line. Independent evidence indicates that, over this dose range, ethylnitrosourea reaches the testis in amounts directly proportional to the injected dose. It is concluded that, despite the mutagenic effectiveness of ethylnitrosourea, the spermatogonia are apparently capable of repairing at least a major part of the mutational damage when the repair process is not swamped by a high dose. This finding is important both in basic studies on the mutagenic action of chemicals in mammals and in risk estimation.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>6954505</pmid><doi>10.1073/pnas.79.11.3589</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
subjects | 550400 - Genetics 560305 - Chemicals Metabolism & Toxicology- Vertebrates- (-1987) Alleles Allelism ANIMALS BASIC BIOLOGICAL SCIENCES BIOLOGICAL EFFECTS BIOLOGICAL RECOVERY BIOLOGICAL REPAIR Confidence limits DATA DNA Repair Dose response relationship Dose-Response Relationship, Drug DOSE-RESPONSE RELATIONSHIPS Ethylnitrosourea - pharmacology EXPERIMENTAL DATA GAMETES GENE MUTATIONS Genetic loci Genetic mutation GERM CELLS INFORMATION Male MAMMALS MICE MUTAGENESIS Mutation - drug effects MUTATION FREQUENCY MUTATIONS NITROSO COMPOUNDS Nitrosourea Compounds - pharmacology NUMERICAL DATA ORGANIC COMPOUNDS ORGANIC NITROGEN COMPOUNDS Radiation dosage RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT RECOVERY REPAIR RISK ASSESSMENT RODENTS SPERMATOGONIA Spermatogonia - drug effects Spermatozoa - drug effects Statistical significance Testes VERTEBRATES |
title | Dose--Response Curve for Ethylnitrosourea-Induced Specific-Locus Mutations in Mouse Spermatogonia |
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