Linked Life Data

10328754

Source:http://linkedlifedata.com/resource/pubmed/id/10328754

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-7-27
pubmed:abstractText
The tumor initiating activities of 4H-cyclopenta[def]chrysene (C[def]C) and its two putative reactive metabolites, trans-1, 2-dihydroxy-anti-3,3a-epoxy-1,2,3, 3a-tetrahydro-4H-cyclopenta[def]chrysene (C[def]C-3,3a-DE) and trans-6,7-dihydroxy-anti-8,9-epoxy-6,7,8, 9-tetrahydro-4H-cyclopenta[def]chrysene (C[def]C-8,9-DE), were evaluated previously in mice [Amin, S., et al. (1995) Carcinogenesis 16, 2813-2817]. C[def]C-3,3a-DE was the more active inducer of lung tumors and elicited twice as many tumors as C[def]C-8,9-DE. In this study, the route of metabolism of C[def]C to DNA-reactive metabolites in the human mammary carcinoma cell line (MCF-7) was investigated using the 32P-postlabeling assay. The results show that metabolic activation to DNA-binding species proceeds through the formation of both trans-1,2-dihydrodiol and trans-6,7-dihydrodiol metabolites of C[def]C. At a 1 microM dose, adducts from the methylene-bridged (C[def]C-3,3a-DE) and bay region (C[def]C-8,9-DE) dihydrodiol epoxides were detected in comparable amounts. In contrast, the majority of the postlabeled adducts recovered from cells exposed to a 10 microM dose were derived from the bay region dihydrodiol epoxide, C[def]C-8,9-DE. Using markers from reactions of the dihydrodiol epoxides with deoxyguanosine 3'-phosphate and deoxyadenosine 3'-phosphate, it was shown that the major radioactive spots formed with both anti-C[def]C-3,3a-DE and anti-C[def]C-8,9-DE chromatographed with deoxyguanosine adduct markers. Thus, the human cells used in these studies can activate C[def]C to carcinogenic metabolites.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
437-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Metabolic activation of 4H-cyclopenta[def]chrysene in human mammary carcinoma MCF-7 cell cultures.
pubmed:affiliation
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. agarwalr@intra.nci.nih.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't