The combined antiandrogenic effects of five commonly used pesticides
In this study, mixture effects of five dissimilarly acting pesticides were analyzed for antiandrogenic effects in vitro and in vivo. Deltamethrin, methiocarb, prochloraz, simazine, and tribenuron-methyl are all commonly used for agricultural and horticultural purposes. Concentration–response curves...
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| Veröffentlicht in: | Toxicology and applied pharmacology 2004-11, Vol.201 (1), p.10-20 |
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| creator | Birkhøj, Mia Nellemann, Christine Jarfelt, Kirsten Jacobsen, Helene Andersen, Helle Raun Dalgaard, Majken Vinggaard, Anne Marie |
| description | In this study, mixture effects of five dissimilarly acting pesticides were analyzed for antiandrogenic effects in vitro and in vivo. Deltamethrin, methiocarb, prochloraz, simazine, and tribenuron-methyl are all commonly used for agricultural and horticultural purposes.
Concentration–response curves for the inhibition of R1881-induced transcriptional activity of the androgen receptor (AR) in vitro of each pesticide alone and in an equimolar mixture were obtained. The IC
25 values for deltamethrin, methiocarb, prochloraz, and the mixture were 5.8, 5.8, 3.5, and 7.5 μM, respectively. Simazine and tribenuron-methyl were ineffective. Applying the isobole method resulted in an isobole coefficient of 0.94 at IC
25 for the effect of the mixture, indicating additive effects of the compounds. Comparison of observed effects and effects calculated by assuming additivity also strongly indicated additive effects of the pesticides in vitro. In vivo, each of the five pesticides and a mixture of the pesticides were tested for antiandrogenic effects in castrated testosterone-treated Wistar rats. The mixture induced a significant change of weights of the levator ani/bulbocavernosus muscle and adrenal glands. Changes in gene expression in ventral prostates were observed as distinct effects on levels of ornithin decarboxylase (ODC) mRNA and effects on levels of prostate binding protein subunit C3 (PBP C3) mRNA. No pesticide-induced effect on the level of testosterone-repressed prostatic message 2 (TRPM-2) mRNA was observed, whereas flutamide increased TRPM-2 levels.
In conclusion, the pesticides were found to act additively in vitro. In vivo, the organ weight changes indicated that the pesticides had an accumulating effect that was not observed for the individual pesticides. Several pesticide-induced gene expression changes were observed, indicating that these are either very sensitive antiandrogenic end-points or that these changes are induced by a pathway not related to AR. |
| doi_str_mv | 10.1016/j.taap.2004.04.016 |
| format | Article |
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Concentration–response curves for the inhibition of R1881-induced transcriptional activity of the androgen receptor (AR) in vitro of each pesticide alone and in an equimolar mixture were obtained. The IC
25 values for deltamethrin, methiocarb, prochloraz, and the mixture were 5.8, 5.8, 3.5, and 7.5 μM, respectively. Simazine and tribenuron-methyl were ineffective. Applying the isobole method resulted in an isobole coefficient of 0.94 at IC
25 for the effect of the mixture, indicating additive effects of the compounds. Comparison of observed effects and effects calculated by assuming additivity also strongly indicated additive effects of the pesticides in vitro. In vivo, each of the five pesticides and a mixture of the pesticides were tested for antiandrogenic effects in castrated testosterone-treated Wistar rats. The mixture induced a significant change of weights of the levator ani/bulbocavernosus muscle and adrenal glands. Changes in gene expression in ventral prostates were observed as distinct effects on levels of ornithin decarboxylase (ODC) mRNA and effects on levels of prostate binding protein subunit C3 (PBP C3) mRNA. No pesticide-induced effect on the level of testosterone-repressed prostatic message 2 (TRPM-2) mRNA was observed, whereas flutamide increased TRPM-2 levels.
In conclusion, the pesticides were found to act additively in vitro. In vivo, the organ weight changes indicated that the pesticides had an accumulating effect that was not observed for the individual pesticides. Several pesticide-induced gene expression changes were observed, indicating that these are either very sensitive antiandrogenic end-points or that these changes are induced by a pathway not related to AR.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2004.04.016</identifier><identifier>PMID: 15519604</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Androgen Antagonists - toxicity ; Androgen Receptor Antagonists ; Androgens ; Animals ; Antiandrogen ; Biological and medical sciences ; Concentration addition ; Deltamethrin ; DNA, Complementary - biosynthesis ; Dose-Response Relationship, Drug ; Drug Interactions ; Endocrine disrupters ; Gene expression ; Genes, Reporter - drug effects ; Genes, Reporter - genetics ; Isobole Method ; Male ; Medical sciences ; Methiocarb ; Mixture effects ; Orchiectomy ; Organ Size - drug effects ; Pesticides - toxicity ; Pesticides, fertilizers and other agrochemicals toxicology ; Prochloraz ; Prostate - drug effects ; Prostate - metabolism ; Rats ; Rats, Wistar ; Receptors, Androgen ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - isolation & purification ; Simazine ; Testosterone - blood ; Toxicology ; Tribenuron-methyl</subject><ispartof>Toxicology and applied pharmacology, 2004-11, Vol.201 (1), p.10-20</ispartof><rights>2004 Elsevier Inc.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-b9d13c9c63882d869eebf1636ab704536679de06936c3a27fbed5744a0043d803</citedby><cites>FETCH-LOGICAL-c479t-b9d13c9c63882d869eebf1636ab704536679de06936c3a27fbed5744a0043d803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2004.04.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16266703$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15519604$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Birkhøj, Mia</creatorcontrib><creatorcontrib>Nellemann, Christine</creatorcontrib><creatorcontrib>Jarfelt, Kirsten</creatorcontrib><creatorcontrib>Jacobsen, Helene</creatorcontrib><creatorcontrib>Andersen, Helle Raun</creatorcontrib><creatorcontrib>Dalgaard, Majken</creatorcontrib><creatorcontrib>Vinggaard, Anne Marie</creatorcontrib><title>The combined antiandrogenic effects of five commonly used pesticides</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>In this study, mixture effects of five dissimilarly acting pesticides were analyzed for antiandrogenic effects in vitro and in vivo. Deltamethrin, methiocarb, prochloraz, simazine, and tribenuron-methyl are all commonly used for agricultural and horticultural purposes.
Concentration–response curves for the inhibition of R1881-induced transcriptional activity of the androgen receptor (AR) in vitro of each pesticide alone and in an equimolar mixture were obtained. The IC
25 values for deltamethrin, methiocarb, prochloraz, and the mixture were 5.8, 5.8, 3.5, and 7.5 μM, respectively. Simazine and tribenuron-methyl were ineffective. Applying the isobole method resulted in an isobole coefficient of 0.94 at IC
25 for the effect of the mixture, indicating additive effects of the compounds. Comparison of observed effects and effects calculated by assuming additivity also strongly indicated additive effects of the pesticides in vitro. In vivo, each of the five pesticides and a mixture of the pesticides were tested for antiandrogenic effects in castrated testosterone-treated Wistar rats. The mixture induced a significant change of weights of the levator ani/bulbocavernosus muscle and adrenal glands. Changes in gene expression in ventral prostates were observed as distinct effects on levels of ornithin decarboxylase (ODC) mRNA and effects on levels of prostate binding protein subunit C3 (PBP C3) mRNA. No pesticide-induced effect on the level of testosterone-repressed prostatic message 2 (TRPM-2) mRNA was observed, whereas flutamide increased TRPM-2 levels.
In conclusion, the pesticides were found to act additively in vitro. In vivo, the organ weight changes indicated that the pesticides had an accumulating effect that was not observed for the individual pesticides. Several pesticide-induced gene expression changes were observed, indicating that these are either very sensitive antiandrogenic end-points or that these changes are induced by a pathway not related to AR.</description><subject>Androgen Antagonists - toxicity</subject><subject>Androgen Receptor Antagonists</subject><subject>Androgens</subject><subject>Animals</subject><subject>Antiandrogen</subject><subject>Biological and medical sciences</subject><subject>Concentration addition</subject><subject>Deltamethrin</subject><subject>DNA, Complementary - biosynthesis</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Interactions</subject><subject>Endocrine disrupters</subject><subject>Gene expression</subject><subject>Genes, Reporter - drug effects</subject><subject>Genes, Reporter - genetics</subject><subject>Isobole Method</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methiocarb</subject><subject>Mixture effects</subject><subject>Orchiectomy</subject><subject>Organ Size - drug effects</subject><subject>Pesticides - toxicity</subject><subject>Pesticides, fertilizers and other agrochemicals toxicology</subject><subject>Prochloraz</subject><subject>Prostate - drug effects</subject><subject>Prostate - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Androgen</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - isolation & purification</subject><subject>Simazine</subject><subject>Testosterone - blood</subject><subject>Toxicology</subject><subject>Tribenuron-methyl</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLAzEQgIMotlb_gAfZi962Tjbb7Aa8SH1CwUsFbyGbTDRlHzXZFvrvzdqCN2FgDvPN6yPkksKUAuW3q2mv1HqaAeTTISg_ImMKgqfAGDsm41igKUD5MSJnIawAQOQ5PSUjOptRwSEfk4flFya6ayrXoklU2zvVGt99Yut0gtai7kPS2cS67S_XdG29SzYhwmsMvdPOYDgnJ1bVAS8OeULenx6X85d08fb8Or9fpDovRJ9WwlCmheasLDNTcoFYWcoZV1UB-YxxXgiDwAXjmqmssBWaWZHnKv7BTAlsQm72c9e--97E9bJxQWNdqxa7TZC0KErOoYxgtge170LwaOXau0b5naQgB3dyJQd3cnAnh4hnTMjVYfqmatD8tRxkReD6AKigVW29arULfxzP4gdR_YTc7TmMLrYOvQzaYavROB99StO5_-74AVpKjEw</recordid><startdate>20041115</startdate><enddate>20041115</enddate><creator>Birkhøj, Mia</creator><creator>Nellemann, Christine</creator><creator>Jarfelt, Kirsten</creator><creator>Jacobsen, Helene</creator><creator>Andersen, Helle Raun</creator><creator>Dalgaard, Majken</creator><creator>Vinggaard, Anne Marie</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>7U7</scope><scope>C1K</scope></search><sort><creationdate>20041115</creationdate><title>The combined antiandrogenic effects of five commonly used pesticides</title><author>Birkhøj, Mia ; Nellemann, Christine ; Jarfelt, Kirsten ; Jacobsen, Helene ; Andersen, Helle Raun ; Dalgaard, Majken ; Vinggaard, Anne Marie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-b9d13c9c63882d869eebf1636ab704536679de06936c3a27fbed5744a0043d803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Androgen Antagonists - toxicity</topic><topic>Androgen Receptor Antagonists</topic><topic>Androgens</topic><topic>Animals</topic><topic>Antiandrogen</topic><topic>Biological and medical sciences</topic><topic>Concentration addition</topic><topic>Deltamethrin</topic><topic>DNA, Complementary - biosynthesis</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Interactions</topic><topic>Endocrine disrupters</topic><topic>Gene expression</topic><topic>Genes, Reporter - drug effects</topic><topic>Genes, Reporter - genetics</topic><topic>Isobole Method</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methiocarb</topic><topic>Mixture effects</topic><topic>Orchiectomy</topic><topic>Organ Size - drug effects</topic><topic>Pesticides - toxicity</topic><topic>Pesticides, fertilizers and other agrochemicals toxicology</topic><topic>Prochloraz</topic><topic>Prostate - drug effects</topic><topic>Prostate - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Androgen</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - isolation & purification</topic><topic>Simazine</topic><topic>Testosterone - blood</topic><topic>Toxicology</topic><topic>Tribenuron-methyl</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Birkhøj, Mia</creatorcontrib><creatorcontrib>Nellemann, Christine</creatorcontrib><creatorcontrib>Jarfelt, Kirsten</creatorcontrib><creatorcontrib>Jacobsen, Helene</creatorcontrib><creatorcontrib>Andersen, Helle Raun</creatorcontrib><creatorcontrib>Dalgaard, Majken</creatorcontrib><creatorcontrib>Vinggaard, Anne Marie</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Birkhøj, Mia</au><au>Nellemann, Christine</au><au>Jarfelt, Kirsten</au><au>Jacobsen, Helene</au><au>Andersen, Helle Raun</au><au>Dalgaard, Majken</au><au>Vinggaard, Anne Marie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The combined antiandrogenic effects of five commonly used pesticides</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2004-11-15</date><risdate>2004</risdate><volume>201</volume><issue>1</issue><spage>10</spage><epage>20</epage><pages>10-20</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>In this study, mixture effects of five dissimilarly acting pesticides were analyzed for antiandrogenic effects in vitro and in vivo. Deltamethrin, methiocarb, prochloraz, simazine, and tribenuron-methyl are all commonly used for agricultural and horticultural purposes.
Concentration–response curves for the inhibition of R1881-induced transcriptional activity of the androgen receptor (AR) in vitro of each pesticide alone and in an equimolar mixture were obtained. The IC
25 values for deltamethrin, methiocarb, prochloraz, and the mixture were 5.8, 5.8, 3.5, and 7.5 μM, respectively. Simazine and tribenuron-methyl were ineffective. Applying the isobole method resulted in an isobole coefficient of 0.94 at IC
25 for the effect of the mixture, indicating additive effects of the compounds. Comparison of observed effects and effects calculated by assuming additivity also strongly indicated additive effects of the pesticides in vitro. In vivo, each of the five pesticides and a mixture of the pesticides were tested for antiandrogenic effects in castrated testosterone-treated Wistar rats. The mixture induced a significant change of weights of the levator ani/bulbocavernosus muscle and adrenal glands. Changes in gene expression in ventral prostates were observed as distinct effects on levels of ornithin decarboxylase (ODC) mRNA and effects on levels of prostate binding protein subunit C3 (PBP C3) mRNA. No pesticide-induced effect on the level of testosterone-repressed prostatic message 2 (TRPM-2) mRNA was observed, whereas flutamide increased TRPM-2 levels.
In conclusion, the pesticides were found to act additively in vitro. In vivo, the organ weight changes indicated that the pesticides had an accumulating effect that was not observed for the individual pesticides. Several pesticide-induced gene expression changes were observed, indicating that these are either very sensitive antiandrogenic end-points or that these changes are induced by a pathway not related to AR.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>15519604</pmid><doi>10.1016/j.taap.2004.04.016</doi><tpages>11</tpages></addata></record> |
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| subjects | Androgen Antagonists - toxicity Androgen Receptor Antagonists Androgens Animals Antiandrogen Biological and medical sciences Concentration addition Deltamethrin DNA, Complementary - biosynthesis Dose-Response Relationship, Drug Drug Interactions Endocrine disrupters Gene expression Genes, Reporter - drug effects Genes, Reporter - genetics Isobole Method Male Medical sciences Methiocarb Mixture effects Orchiectomy Organ Size - drug effects Pesticides - toxicity Pesticides, fertilizers and other agrochemicals toxicology Prochloraz Prostate - drug effects Prostate - metabolism Rats Rats, Wistar Receptors, Androgen Reverse Transcriptase Polymerase Chain Reaction RNA - isolation & purification Simazine Testosterone - blood Toxicology Tribenuron-methyl |
| title | The combined antiandrogenic effects of five commonly used pesticides |
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