Promotional activities of the non-genotoxic carcinogen bemitradine (SC-33643)
Bemitradine (SC‐33643), a diuretic antihypertensive agent, was studied for its carcinogenicity in a 2‐year bioassay in Charles River CD rats via dietary admix at dosages of 50, 150 and 450 mg kg−1 for up to 97 weeks (after which they were followed for eight additional weeks without treatment). Body...
Gespeichert in:
Veröffentlicht in: | Journal of applied toxicology 1992-06, Vol.12 (3), p.157-164 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 164 |
---|---|
container_issue | 3 |
container_start_page | 157 |
container_title | Journal of applied toxicology |
container_volume | 12 |
creator | Gad, Shayne C. Burton, Earl Chengelis, Christopher P. Levin, Stuart Piper, Charles E. Oshiro, Yuki Semler, David E. |
description | Bemitradine (SC‐33643), a diuretic antihypertensive agent, was studied for its carcinogenicity in a 2‐year bioassay in Charles River CD rats via dietary admix at dosages of 50, 150 and 450 mg kg−1 for up to 97 weeks (after which they were followed for eight additional weeks without treatment). Body weights were decreased compared to controls: 5–15% in the female and 10–12% in the male dosage groups by week 105 of the study. Prolactin values were significantly increased in 150 and 450 mg kg−1 females. The compound caused significant increased incidences of liver, thyroid (both sexes) and mammary (females only) neoplasms.
The metabolism of bemitradine was studied in both rats and man. Bemitradine and its primary metabolite (SC‐36741; desethylbemitradine) were tested and found to be non‐genotoxic in Ames, rat primary hepatocyte UDS, CHO/HGPRT, CHO cytogenetics, in vivo mouse micronucleus and mouse lymphoma TK+/− (bemitradine only) assays.
Finally, in an altered hepatic foci (Y‐glutamyl transpeptidase positive) promotion assay in female Charles River CD rats, bemitradine was found to be a promotor, though not as potent as phenobarbital.
We concluded that bemitradine (which has been dropped from development) is a non‐genotoxic carcinogen which appears to act by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands. Tumors seen in the thyroid were probably secondary to the effects of bemitradine on metabolism. |
doi_str_mv | 10.1002/jat.2550120303 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_16541637</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>14284066</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3843-44cd2b89616b1f731a797b57576c01548e62bd943d601abeabe16fc3d60a247f3</originalsourceid><addsrcrecordid>eNqFkM1v1DAQxS0EKtvClRtSDgjBIYvHH-PkWK1ooVpKgSJ6sxzHAZckLra3tP89WWXVilMlS5bn_d4b6xHyAugSKGXvLk1eMikpMMopf0QWQOu6BIb8MVlQhrQUXF08JfspXVI6aazaI3uArJYAC_LpLIYhZB9G0xfGZn_ts3epCF2Rf7liDGP5040hhxtvC2ui9WOYBkXjBp-jaf3oijffViXnKPjbZ-RJZ_rknu_uA_L96P356kO5_nz8cXW4Li2vBC-FsC1rqhoBG-gUB6Nq1UglFVoKUlQOWdPWgrdIwTRuOoCd3T4NE6rjB-T1nHsVw5-NS1kPPlnX92Z0YZM0oBSAXD0MClYJijiByxm0MaQUXaevoh9MvNVA9bZoPRWt74ueDC93yZtmcO09Pjc76a92uknW9F00o_XpDpMMZc22WD1jf33vbh9Yqk8Oz__7Qjl7fcru5s5r4m-Niiupf5wea_x6-uVofXGiz_g_QDGjqw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>14284066</pqid></control><display><type>article</type><title>Promotional activities of the non-genotoxic carcinogen bemitradine (SC-33643)</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Gad, Shayne C. ; Burton, Earl ; Chengelis, Christopher P. ; Levin, Stuart ; Piper, Charles E. ; Oshiro, Yuki ; Semler, David E.</creator><creatorcontrib>Gad, Shayne C. ; Burton, Earl ; Chengelis, Christopher P. ; Levin, Stuart ; Piper, Charles E. ; Oshiro, Yuki ; Semler, David E.</creatorcontrib><description>Bemitradine (SC‐33643), a diuretic antihypertensive agent, was studied for its carcinogenicity in a 2‐year bioassay in Charles River CD rats via dietary admix at dosages of 50, 150 and 450 mg kg−1 for up to 97 weeks (after which they were followed for eight additional weeks without treatment). Body weights were decreased compared to controls: 5–15% in the female and 10–12% in the male dosage groups by week 105 of the study. Prolactin values were significantly increased in 150 and 450 mg kg−1 females. The compound caused significant increased incidences of liver, thyroid (both sexes) and mammary (females only) neoplasms.
The metabolism of bemitradine was studied in both rats and man. Bemitradine and its primary metabolite (SC‐36741; desethylbemitradine) were tested and found to be non‐genotoxic in Ames, rat primary hepatocyte UDS, CHO/HGPRT, CHO cytogenetics, in vivo mouse micronucleus and mouse lymphoma TK+/− (bemitradine only) assays.
Finally, in an altered hepatic foci (Y‐glutamyl transpeptidase positive) promotion assay in female Charles River CD rats, bemitradine was found to be a promotor, though not as potent as phenobarbital.
We concluded that bemitradine (which has been dropped from development) is a non‐genotoxic carcinogen which appears to act by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands. Tumors seen in the thyroid were probably secondary to the effects of bemitradine on metabolism.</description><identifier>ISSN: 0260-437X</identifier><identifier>EISSN: 1099-1263</identifier><identifier>DOI: 10.1002/jat.2550120303</identifier><identifier>PMID: 1629511</identifier><identifier>CODEN: JJATDK</identifier><language>eng</language><publisher>Chichester: John Wiley & Sons, Ltd</publisher><subject>Animals ; Biological and medical sciences ; carcinogenicity ; Carcinogens - toxicity ; CHO Cells ; Chromosome Aberrations ; Cricetinae ; Drug toxicity and drugs side effects treatment ; genotoxicity ; Hypoxanthine Phosphoribosyltransferase - genetics ; In Vitro Techniques ; Liver Neoplasms, Experimental - chemically induced ; Liver Neoplasms, Experimental - pathology ; Lymphoma - genetics ; Medical sciences ; Mice ; Micronucleus Tests ; Miscellaneous (drug allergy, mutagens, teratogens...) ; mutagenicity ; Mutagenicity Tests ; Mutagens - toxicity ; Pharmacology. Drug treatments ; promotion ; Pyrimidines - pharmacokinetics ; Pyrimidines - toxicity ; Rats ; Salmonella typhimurium - genetics ; Triazoles - pharmacokinetics ; Triazoles - toxicity</subject><ispartof>Journal of applied toxicology, 1992-06, Vol.12 (3), p.157-164</ispartof><rights>Copyright © 1992 John Wiley & Sons, Ltd.</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3843-44cd2b89616b1f731a797b57576c01548e62bd943d601abeabe16fc3d60a247f3</citedby><cites>FETCH-LOGICAL-c3843-44cd2b89616b1f731a797b57576c01548e62bd943d601abeabe16fc3d60a247f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjat.2550120303$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjat.2550120303$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5265921$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1629511$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gad, Shayne C.</creatorcontrib><creatorcontrib>Burton, Earl</creatorcontrib><creatorcontrib>Chengelis, Christopher P.</creatorcontrib><creatorcontrib>Levin, Stuart</creatorcontrib><creatorcontrib>Piper, Charles E.</creatorcontrib><creatorcontrib>Oshiro, Yuki</creatorcontrib><creatorcontrib>Semler, David E.</creatorcontrib><title>Promotional activities of the non-genotoxic carcinogen bemitradine (SC-33643)</title><title>Journal of applied toxicology</title><addtitle>J. Appl. Toxicol</addtitle><description>Bemitradine (SC‐33643), a diuretic antihypertensive agent, was studied for its carcinogenicity in a 2‐year bioassay in Charles River CD rats via dietary admix at dosages of 50, 150 and 450 mg kg−1 for up to 97 weeks (after which they were followed for eight additional weeks without treatment). Body weights were decreased compared to controls: 5–15% in the female and 10–12% in the male dosage groups by week 105 of the study. Prolactin values were significantly increased in 150 and 450 mg kg−1 females. The compound caused significant increased incidences of liver, thyroid (both sexes) and mammary (females only) neoplasms.
The metabolism of bemitradine was studied in both rats and man. Bemitradine and its primary metabolite (SC‐36741; desethylbemitradine) were tested and found to be non‐genotoxic in Ames, rat primary hepatocyte UDS, CHO/HGPRT, CHO cytogenetics, in vivo mouse micronucleus and mouse lymphoma TK+/− (bemitradine only) assays.
Finally, in an altered hepatic foci (Y‐glutamyl transpeptidase positive) promotion assay in female Charles River CD rats, bemitradine was found to be a promotor, though not as potent as phenobarbital.
We concluded that bemitradine (which has been dropped from development) is a non‐genotoxic carcinogen which appears to act by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands. Tumors seen in the thyroid were probably secondary to the effects of bemitradine on metabolism.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>carcinogenicity</subject><subject>Carcinogens - toxicity</subject><subject>CHO Cells</subject><subject>Chromosome Aberrations</subject><subject>Cricetinae</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>genotoxicity</subject><subject>Hypoxanthine Phosphoribosyltransferase - genetics</subject><subject>In Vitro Techniques</subject><subject>Liver Neoplasms, Experimental - chemically induced</subject><subject>Liver Neoplasms, Experimental - pathology</subject><subject>Lymphoma - genetics</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Micronucleus Tests</subject><subject>Miscellaneous (drug allergy, mutagens, teratogens...)</subject><subject>mutagenicity</subject><subject>Mutagenicity Tests</subject><subject>Mutagens - toxicity</subject><subject>Pharmacology. Drug treatments</subject><subject>promotion</subject><subject>Pyrimidines - pharmacokinetics</subject><subject>Pyrimidines - toxicity</subject><subject>Rats</subject><subject>Salmonella typhimurium - genetics</subject><subject>Triazoles - pharmacokinetics</subject><subject>Triazoles - toxicity</subject><issn>0260-437X</issn><issn>1099-1263</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1v1DAQxS0EKtvClRtSDgjBIYvHH-PkWK1ooVpKgSJ6sxzHAZckLra3tP89WWXVilMlS5bn_d4b6xHyAugSKGXvLk1eMikpMMopf0QWQOu6BIb8MVlQhrQUXF08JfspXVI6aazaI3uArJYAC_LpLIYhZB9G0xfGZn_ts3epCF2Rf7liDGP5040hhxtvC2ui9WOYBkXjBp-jaf3oijffViXnKPjbZ-RJZ_rknu_uA_L96P356kO5_nz8cXW4Li2vBC-FsC1rqhoBG-gUB6Nq1UglFVoKUlQOWdPWgrdIwTRuOoCd3T4NE6rjB-T1nHsVw5-NS1kPPlnX92Z0YZM0oBSAXD0MClYJijiByxm0MaQUXaevoh9MvNVA9bZoPRWt74ueDC93yZtmcO09Pjc76a92uknW9F00o_XpDpMMZc22WD1jf33vbh9Yqk8Oz__7Qjl7fcru5s5r4m-Niiupf5wea_x6-uVofXGiz_g_QDGjqw</recordid><startdate>199206</startdate><enddate>199206</enddate><creator>Gad, Shayne C.</creator><creator>Burton, Earl</creator><creator>Chengelis, Christopher P.</creator><creator>Levin, Stuart</creator><creator>Piper, Charles E.</creator><creator>Oshiro, Yuki</creator><creator>Semler, David E.</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</scope><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>7ST</scope><scope>C1K</scope><scope>SOI</scope><scope>7U7</scope></search><sort><creationdate>199206</creationdate><title>Promotional activities of the non-genotoxic carcinogen bemitradine (SC-33643)</title><author>Gad, Shayne C. ; Burton, Earl ; Chengelis, Christopher P. ; Levin, Stuart ; Piper, Charles E. ; Oshiro, Yuki ; Semler, David E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3843-44cd2b89616b1f731a797b57576c01548e62bd943d601abeabe16fc3d60a247f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>carcinogenicity</topic><topic>Carcinogens - toxicity</topic><topic>CHO Cells</topic><topic>Chromosome Aberrations</topic><topic>Cricetinae</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>genotoxicity</topic><topic>Hypoxanthine Phosphoribosyltransferase - genetics</topic><topic>In Vitro Techniques</topic><topic>Liver Neoplasms, Experimental - chemically induced</topic><topic>Liver Neoplasms, Experimental - pathology</topic><topic>Lymphoma - genetics</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Micronucleus Tests</topic><topic>Miscellaneous (drug allergy, mutagens, teratogens...)</topic><topic>mutagenicity</topic><topic>Mutagenicity Tests</topic><topic>Mutagens - toxicity</topic><topic>Pharmacology. Drug treatments</topic><topic>promotion</topic><topic>Pyrimidines - pharmacokinetics</topic><topic>Pyrimidines - toxicity</topic><topic>Rats</topic><topic>Salmonella typhimurium - genetics</topic><topic>Triazoles - pharmacokinetics</topic><topic>Triazoles - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gad, Shayne C.</creatorcontrib><creatorcontrib>Burton, Earl</creatorcontrib><creatorcontrib>Chengelis, Christopher P.</creatorcontrib><creatorcontrib>Levin, Stuart</creatorcontrib><creatorcontrib>Piper, Charles E.</creatorcontrib><creatorcontrib>Oshiro, Yuki</creatorcontrib><creatorcontrib>Semler, David E.</creatorcontrib><collection>Istex</collection><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>Environment Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><jtitle>Journal of applied toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gad, Shayne C.</au><au>Burton, Earl</au><au>Chengelis, Christopher P.</au><au>Levin, Stuart</au><au>Piper, Charles E.</au><au>Oshiro, Yuki</au><au>Semler, David E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Promotional activities of the non-genotoxic carcinogen bemitradine (SC-33643)</atitle><jtitle>Journal of applied toxicology</jtitle><addtitle>J. Appl. Toxicol</addtitle><date>1992-06</date><risdate>1992</risdate><volume>12</volume><issue>3</issue><spage>157</spage><epage>164</epage><pages>157-164</pages><issn>0260-437X</issn><eissn>1099-1263</eissn><coden>JJATDK</coden><abstract>Bemitradine (SC‐33643), a diuretic antihypertensive agent, was studied for its carcinogenicity in a 2‐year bioassay in Charles River CD rats via dietary admix at dosages of 50, 150 and 450 mg kg−1 for up to 97 weeks (after which they were followed for eight additional weeks without treatment). Body weights were decreased compared to controls: 5–15% in the female and 10–12% in the male dosage groups by week 105 of the study. Prolactin values were significantly increased in 150 and 450 mg kg−1 females. The compound caused significant increased incidences of liver, thyroid (both sexes) and mammary (females only) neoplasms.
The metabolism of bemitradine was studied in both rats and man. Bemitradine and its primary metabolite (SC‐36741; desethylbemitradine) were tested and found to be non‐genotoxic in Ames, rat primary hepatocyte UDS, CHO/HGPRT, CHO cytogenetics, in vivo mouse micronucleus and mouse lymphoma TK+/− (bemitradine only) assays.
Finally, in an altered hepatic foci (Y‐glutamyl transpeptidase positive) promotion assay in female Charles River CD rats, bemitradine was found to be a promotor, though not as potent as phenobarbital.
We concluded that bemitradine (which has been dropped from development) is a non‐genotoxic carcinogen which appears to act by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands. Tumors seen in the thyroid were probably secondary to the effects of bemitradine on metabolism.</abstract><cop>Chichester</cop><pub>John Wiley & Sons, Ltd</pub><pmid>1629511</pmid><doi>10.1002/jat.2550120303</doi><tpages>8</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0260-437X |
ispartof | Journal of applied toxicology, 1992-06, Vol.12 (3), p.157-164 |
issn | 0260-437X 1099-1263 |
language | eng |
recordid | cdi_proquest_miscellaneous_16541637 |
source | MEDLINE; Wiley Online Library All Journals |
subjects | Animals Biological and medical sciences carcinogenicity Carcinogens - toxicity CHO Cells Chromosome Aberrations Cricetinae Drug toxicity and drugs side effects treatment genotoxicity Hypoxanthine Phosphoribosyltransferase - genetics In Vitro Techniques Liver Neoplasms, Experimental - chemically induced Liver Neoplasms, Experimental - pathology Lymphoma - genetics Medical sciences Mice Micronucleus Tests Miscellaneous (drug allergy, mutagens, teratogens...) mutagenicity Mutagenicity Tests Mutagens - toxicity Pharmacology. Drug treatments promotion Pyrimidines - pharmacokinetics Pyrimidines - toxicity Rats Salmonella typhimurium - genetics Triazoles - pharmacokinetics Triazoles - toxicity |
title | Promotional activities of the non-genotoxic carcinogen bemitradine (SC-33643) |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-10T13%3A45%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Promotional%20activities%20of%20the%20non-genotoxic%20carcinogen%20bemitradine%20(SC-33643)&rft.jtitle=Journal%20of%20applied%20toxicology&rft.au=Gad,%20Shayne%20C.&rft.date=1992-06&rft.volume=12&rft.issue=3&rft.spage=157&rft.epage=164&rft.pages=157-164&rft.issn=0260-437X&rft.eissn=1099-1263&rft.coden=JJATDK&rft_id=info:doi/10.1002/jat.2550120303&rft_dat=%3Cproquest_cross%3E14284066%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=14284066&rft_id=info:pmid/1629511&rfr_iscdi=true |