Leukemia induced in rats but not mice by dimethyl morpholinophosphoramidate, a simulant anticholinesterase agent
Dimethyl morpholinophosphoramidate (DMMPA), an organophosphate, caused leukemia in male and female Fischer 344/N rats. DMMPA was administered in corn oil by oral intubation to groups of 50 male and 50 female rats at 0, 150, 300, or 600 mg/kg body weight, five times per week for 2 years. B6C3F1 mice...
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| Veröffentlicht in: | Toxicology (Amsterdam) 1994-07, Vol.91 (2), p.127-137 |
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| creator | Chan, Po Cardy, Richard Haseman, Joseph Moe, James Huff, James |
| description | Dimethyl morpholinophosphoramidate (DMMPA), an organophosphate, caused leukemia in male and female Fischer 344/N rats. DMMPA was administered in corn oil by oral intubation to groups of 50 male and 50 female rats at 0, 150, 300, or 600 mg/kg body weight, five times per week for 2 years. B6C3F1 mice were given 0, 150 (males only), 300, and 600 (females only) mg/kg body weight under the same schedule. DMMPA induced a dose-related enhancement in the incidence of mononuclear cell leukemia in rats—
males:controls =
41
50
, 150
mg
group =
21
50
; 300
mg group =
sol19
50
; 600
mg group =
25
50
;
females: controls =
9
50
, 150
mg
group =
21
50
; 300
mg group =
12
49
; 600
mg group =
18
50
. Survival-adjusted rates strenthen the DMMPA effect: males — 31%, 50%, 47%, and 63%; females — 20%, 32%, 30%, 50%. Latent periods for mononuclear cell leukemia development in exposed rats were not shortened compared to controls. No carcinogenic effects in mice were detected. DMMPA was not mutagenic in
Salmonella, was mutagenic for mouse lymphoma cells, and induced both chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. |
| doi_str_mv | 10.1016/0300-483X(94)90139-2 |
| format | Article |
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males:controls =
41
50
, 150
mg
group =
21
50
; 300
mg group =
sol19
50
; 600
mg group =
25
50
;
females: controls =
9
50
, 150
mg
group =
21
50
; 300
mg group =
12
49
; 600
mg group =
18
50
. Survival-adjusted rates strenthen the DMMPA effect: males — 31%, 50%, 47%, and 63%; females — 20%, 32%, 30%, 50%. Latent periods for mononuclear cell leukemia development in exposed rats were not shortened compared to controls. No carcinogenic effects in mice were detected. DMMPA was not mutagenic in
Salmonella, was mutagenic for mouse lymphoma cells, and induced both chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/0300-483X(94)90139-2</identifier><identifier>PMID: 8059437</identifier><identifier>CODEN: TXICDD</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Administration, Oral ; Animals ; Biological and medical sciences ; Body Weight - drug effects ; Carcinogenesis bioassay ; Carcinogenesis, carcinogens and anticarcinogens ; Carcinogens - toxicity ; Chemical agents ; Dimethyl morpholinophosphoramidate ; Dose-Response Relationship, Drug ; Female ; Glycerophospholipids ; Leukemia in rats ; Leukemia, Experimental - chemically induced ; Leukemia, Experimental - classification ; Liver - drug effects ; Liver - pathology ; Male ; Medical sciences ; Mice ; Organophosphate ; Phosphatidic Acids - toxicity ; Rats ; Rats, Inbred F344 ; Sex Factors ; Species Specificity ; Tumors</subject><ispartof>Toxicology (Amsterdam), 1994-07, Vol.91 (2), p.127-137</ispartof><rights>1994</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-6029973d7dd3eecbc2c6380fcc48ded7e8d604361117cfecbf437cd062c9c46c3</citedby><cites>FETCH-LOGICAL-c448t-6029973d7dd3eecbc2c6380fcc48ded7e8d604361117cfecbf437cd062c9c46c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0300483X94901392$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4259144$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8059437$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chan, Po</creatorcontrib><creatorcontrib>Cardy, Richard</creatorcontrib><creatorcontrib>Haseman, Joseph</creatorcontrib><creatorcontrib>Moe, James</creatorcontrib><creatorcontrib>Huff, James</creatorcontrib><title>Leukemia induced in rats but not mice by dimethyl morpholinophosphoramidate, a simulant anticholinesterase agent</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>Dimethyl morpholinophosphoramidate (DMMPA), an organophosphate, caused leukemia in male and female Fischer 344/N rats. DMMPA was administered in corn oil by oral intubation to groups of 50 male and 50 female rats at 0, 150, 300, or 600 mg/kg body weight, five times per week for 2 years. B6C3F1 mice were given 0, 150 (males only), 300, and 600 (females only) mg/kg body weight under the same schedule. DMMPA induced a dose-related enhancement in the incidence of mononuclear cell leukemia in rats—
males:controls =
41
50
, 150
mg
group =
21
50
; 300
mg group =
sol19
50
; 600
mg group =
25
50
;
females: controls =
9
50
, 150
mg
group =
21
50
; 300
mg group =
12
49
; 600
mg group =
18
50
. Survival-adjusted rates strenthen the DMMPA effect: males — 31%, 50%, 47%, and 63%; females — 20%, 32%, 30%, 50%. Latent periods for mononuclear cell leukemia development in exposed rats were not shortened compared to controls. No carcinogenic effects in mice were detected. DMMPA was not mutagenic in
Salmonella, was mutagenic for mouse lymphoma cells, and induced both chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Body Weight - drug effects</subject><subject>Carcinogenesis bioassay</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Carcinogens - toxicity</subject><subject>Chemical agents</subject><subject>Dimethyl morpholinophosphoramidate</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Glycerophospholipids</subject><subject>Leukemia in rats</subject><subject>Leukemia, Experimental - chemically induced</subject><subject>Leukemia, Experimental - classification</subject><subject>Liver - drug effects</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Organophosphate</subject><subject>Phosphatidic Acids - toxicity</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Sex Factors</subject><subject>Species Specificity</subject><subject>Tumors</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdFrFDEQxkNR6rX2P6iQB5EWXE02uWzyUpDSqnDgi4JvITeZbaOb3TPJCvffN9c77lEfhu9hfjOZfB8hl5x94Iyrj0ww1kgtfl4ZeW0YF6ZpT8iC6840guvlC7I4Iq_IWc6_GGOtkOqUnGq2NFJ0C7JZ4fwbY3A0jH4G9FVpciXT9VzoOBUaAyBdb6kPEcvjdqBxSpvHaQjjVCXXSi4G7wq-p47mEOfBjYXWCvCMYS6YXEbqHnAsr8nL3g0ZLw56Tn7c332__dKsvn3-evtp1YCUujSKtcZ0wnfeC0RYQwtKaNYDSO3Rd6i9YlIoznkHfQX6-h3wTLVgQCoQ5-Tdfu8mTX_meoONIQMO9Tic5my5WmqlO_F_sL4iuVAVlHsQ0pRzwt5uUogubS1ndpeI3dltd3ZbI-1zIratY28O--d1RH8cOkRQ-28PfZfBDX1yI4R8xGS7NFzKit3sMaym_Q2YbIaAY00sJIRi_RT-fccTunmqLQ</recordid><startdate>19940701</startdate><enddate>19940701</enddate><creator>Chan, Po</creator><creator>Cardy, Richard</creator><creator>Haseman, Joseph</creator><creator>Moe, James</creator><creator>Huff, James</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</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>7ST</scope><scope>C1K</scope><scope>SOI</scope><scope>7U7</scope></search><sort><creationdate>19940701</creationdate><title>Leukemia induced in rats but not mice by dimethyl morpholinophosphoramidate, a simulant anticholinesterase agent</title><author>Chan, Po ; Cardy, Richard ; Haseman, Joseph ; Moe, James ; Huff, James</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-6029973d7dd3eecbc2c6380fcc48ded7e8d604361117cfecbf437cd062c9c46c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Body Weight - drug effects</topic><topic>Carcinogenesis bioassay</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Carcinogens - toxicity</topic><topic>Chemical agents</topic><topic>Dimethyl morpholinophosphoramidate</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Glycerophospholipids</topic><topic>Leukemia in rats</topic><topic>Leukemia, Experimental - chemically induced</topic><topic>Leukemia, Experimental - classification</topic><topic>Liver - drug effects</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Organophosphate</topic><topic>Phosphatidic Acids - toxicity</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Sex Factors</topic><topic>Species Specificity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chan, Po</creatorcontrib><creatorcontrib>Cardy, Richard</creatorcontrib><creatorcontrib>Haseman, Joseph</creatorcontrib><creatorcontrib>Moe, James</creatorcontrib><creatorcontrib>Huff, James</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>Environment Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><jtitle>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chan, Po</au><au>Cardy, Richard</au><au>Haseman, Joseph</au><au>Moe, James</au><au>Huff, James</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leukemia induced in rats but not mice by dimethyl morpholinophosphoramidate, a simulant anticholinesterase agent</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>1994-07-01</date><risdate>1994</risdate><volume>91</volume><issue>2</issue><spage>127</spage><epage>137</epage><pages>127-137</pages><issn>0300-483X</issn><eissn>1879-3185</eissn><coden>TXICDD</coden><abstract>Dimethyl morpholinophosphoramidate (DMMPA), an organophosphate, caused leukemia in male and female Fischer 344/N rats. DMMPA was administered in corn oil by oral intubation to groups of 50 male and 50 female rats at 0, 150, 300, or 600 mg/kg body weight, five times per week for 2 years. B6C3F1 mice were given 0, 150 (males only), 300, and 600 (females only) mg/kg body weight under the same schedule. DMMPA induced a dose-related enhancement in the incidence of mononuclear cell leukemia in rats—
males:controls =
41
50
, 150
mg
group =
21
50
; 300
mg group =
sol19
50
; 600
mg group =
25
50
;
females: controls =
9
50
, 150
mg
group =
21
50
; 300
mg group =
12
49
; 600
mg group =
18
50
. Survival-adjusted rates strenthen the DMMPA effect: males — 31%, 50%, 47%, and 63%; females — 20%, 32%, 30%, 50%. Latent periods for mononuclear cell leukemia development in exposed rats were not shortened compared to controls. No carcinogenic effects in mice were detected. DMMPA was not mutagenic in
Salmonella, was mutagenic for mouse lymphoma cells, and induced both chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>8059437</pmid><doi>10.1016/0300-483X(94)90139-2</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0300-483X |
| ispartof | Toxicology (Amsterdam), 1994-07, Vol.91 (2), p.127-137 |
| issn | 0300-483X 1879-3185 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_16586873 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Administration, Oral Animals Biological and medical sciences Body Weight - drug effects Carcinogenesis bioassay Carcinogenesis, carcinogens and anticarcinogens Carcinogens - toxicity Chemical agents Dimethyl morpholinophosphoramidate Dose-Response Relationship, Drug Female Glycerophospholipids Leukemia in rats Leukemia, Experimental - chemically induced Leukemia, Experimental - classification Liver - drug effects Liver - pathology Male Medical sciences Mice Organophosphate Phosphatidic Acids - toxicity Rats Rats, Inbred F344 Sex Factors Species Specificity Tumors |
| title | Leukemia induced in rats but not mice by dimethyl morpholinophosphoramidate, a simulant anticholinesterase agent |
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