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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1989-4-17
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pubmed:abstractText |
Aceanthrylene (ACE), a cyclopenta-fused polycyclic aromatic hydrocarbon (CP-PAH) related to anthracene, has been studied for its ability to be metabolized, to form DNA adducts, and to morphologically transform C3H10T1/2CL8 mouse embryo fibroblasts in culture. Although ACE has been previously shown to be a strong mutagen in Salmonella typhimurium strains TA89 and TA100, it did not transform C3H10T1/2 cells (0.4-16 micrograms/ml) under 2 treatment protocols: treatment (for 24 h) 1 day after seeding the cells; treatment (for 24 h) 5 days after seeding the cells. Both protocols are effective in detecting the morphological transforming activity of PAH and CP-PAH and the latter protocol has been shown to be effective in detecting chemicals which are active in the first protocol only with the additional treatment of the cells with a tumor promoter. ACE is metabolized by C3H10T1/2 cells to ACE-1,2-dihydrodiol (the cyclopenta-ring dihydrodiol) at a rate of 450 pmoles ACE-1,2-dihydrodiol formed/h/10(6) cells. ACE-7,8-dihydrodiol and ACE-9,10-dihydrodiol, identified as major Aroclor-1254-induced rat liver microsomal metabolites from their UV, NMR, and mass spectral data, were not identified in incubations of C3H10T1/2 cells with ACE. ACE-DNA adducts in C3H10T1/2 cells were isolated, separated, identified, and quantitated using the 32P-postlabeling method. ACE forms 4 major adducts and each was identified as an ACE-1,2-oxide/2'-deoxyguanosine adduct. The level of adduction was 2.18 pmoles ACE adducts/mg DNA after a 24-h incubation of ACE (16 micrograms/ml) with C3H10T1/2 cells. ACE-DNA adduct persistence and repair were evaluated in C3H10T1/2 cells using a hydroxyurea block after ACE treatment. ACE-DNA adducts were not repaired under the conditions used in the morphological transformation studies. Thus, ACE provides an interesting example of a mutagenic PAH which is metabolized by C3H10T1/2 cells to active intermediates, forms relatively stable and persistent 2'-deoxyguanosine adducts in C3H10T1/2 cells, and yet induces no detectable morphological transforming activity under the experimental conditions used.
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pubmed:grant | |
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 |
0027-5107
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
222
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
223-35
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2922008-Animals,
pubmed-meshheading:2922008-Anthracenes,
pubmed-meshheading:2922008-Carcinogenicity Tests,
pubmed-meshheading:2922008-Cell Line,
pubmed-meshheading:2922008-Cell Transformation, Neoplastic,
pubmed-meshheading:2922008-DNA,
pubmed-meshheading:2922008-DNA Repair,
pubmed-meshheading:2922008-Fibroblasts,
pubmed-meshheading:2922008-Mice,
pubmed-meshheading:2922008-Mice, Inbred C3H,
pubmed-meshheading:2922008-Microsomes, Liver,
pubmed-meshheading:2922008-Rats
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pubmed:year |
1989
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pubmed:articleTitle |
DNA adduct formation, metabolism, and morphological transforming activity of aceanthrylene in C3H10T1/2CL8 cells.
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pubmed:affiliation |
Carcinogenesis and Metabolism Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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