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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1997-1-27
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pubmed:abstractText |
The probable human carcinogen 4,4'-methylene-bis(2-chloroaniline) (MOCA) was utilized to develop biomarkers of exposure to occupational carcinogens. The 32P postlabeling assay, utilizing the nuclease P1 enhancement procedure, was used to evaluate MOCA-DNA adduct formation in target tissues. Male Sprague-Dawley rats were treated with different dosing regimens of MOCA, and DNA was isolated from the liver. Additionally, a human uroepithelial cell (HUC) line was treated with N-hydroxy-MOCA for 24 hr, cells were harvested, and DNA was isolated. DNA was analyzed for MOCA-DNA adduct formation by the 32P postlabeling assay. Five MOCA adducts were detected in rat liver DNA. Adduct A, which corresponded to N-(deoxyadenosin-8-yl)-4-amino-3-chlorobenzyl alcohol, was the major adduct in rat liver DNA appearing in all treatment groups. Levels of adduct A were higher when MOCA was administered by ip injection versus oral gavage. Phenobarbital pretreatment increased the amount of adduct A approximately 12-fold. The pathway leading to the formation of adduct A in DNA from HUC appeared to be saturated at the concentrations used: 2.5, 5, and 10 microM. However, an additional adduct (E) was observed at the 10 microM treatment level only. A major DNA adduct was detected in the target tissue of rats and target human cells for MOCA-induced carcinogenesis, thus making it useful as a biomarker of exposure. Other DNA adducts were also observed with the different doses and routes of exposure investigated.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0272-0590
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
138-44
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:8812257-Animals,
pubmed-meshheading:8812257-Cells, Cultured,
pubmed-meshheading:8812257-DNA,
pubmed-meshheading:8812257-DNA Adducts,
pubmed-meshheading:8812257-Epithelium,
pubmed-meshheading:8812257-Humans,
pubmed-meshheading:8812257-Liver,
pubmed-meshheading:8812257-Male,
pubmed-meshheading:8812257-Methylenebis(chloroaniline),
pubmed-meshheading:8812257-Mitotic Index,
pubmed-meshheading:8812257-Phosphorus Radioisotopes,
pubmed-meshheading:8812257-Rats,
pubmed-meshheading:8812257-Rats, Sprague-Dawley,
pubmed-meshheading:8812257-Urinary Tract
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pubmed:year |
1996
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pubmed:articleTitle |
Determination of 4,4'-methylene-bis(2-chloroaniline)-DNA adduct formation in rat liver and human uroepithelial cells by the 32P postlabeling assay.
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pubmed:affiliation |
Department of Health and Human Services, National Institute for Occupational Safety and Health, Cincinnati, Ohio 45226, USA.
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pubmed:publicationType |
Journal Article
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