Linked Life Data

10506751

Source:http://linkedlifedata.com/resource/pubmed/id/10506751

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-11-8
pubmed:abstractText
Dibenzo[a,l]pyrene (DB[a,l]P), an extremely potent environmental carcinogen, is metabolically activated in mammalian cells and microsomes through the fjord-region dihydrodiol, trans-DB[a,l]P-11, 12-diol, to syn- and anti-DB[a,l]P-11,12-diol-13,14-epoxides (syn- and anti-DB[a,l]PDEs). The role of seven individual recombinant human cytochrome P450s (1A1, 1A2, 1B1, 2B6, 2C9, 2E1, and 3A4) in the metabolic activation of DB[a,l]P and formation of DNA adducts was examined by using (32)P postlabeling, thin-layer chromatography, and high-pressure liquid chromatography. We found that, in the presence of epoxide hydrolase, only P450 1A1 and P450 1B1 catalyzed the formation of DB[a,l]PDE-DNA adducts and several unidentified polar adducts. Human P450 1A1 catalyzed the formation of DB[a, l]PDE-DNA adducts and unidentified polar adducts at rates threefold and 17-fold greater than did human P450 1B1 (256 fmol/h/nmol P450 versus 90 fmol/h/nmol P450 and 132 fmol/h/nmol P450 versus 8 fmol/h/nmol P450, respectively). P450 1A1 DNA adducts were derived from both anti- and syn-DB[a,l]PDE at rates of 73 fmol/h/nmol P450 and 51 fmol/h/nmol P450, respectively. P450 1B1 produced adducts derived from anti-DB[a,l]PDE at a rate of 82 fmol/h/nmol, whereas only a small number of adducts were derived from syn-DB[a,l]PDE (0.4 fmol/h/nmol). These results demonstrated the potential of human P450 1A1 and P450 1B1 to contribute to the metabolic activation and carcinogenicity of DB[a,l]P and provided additional evidence that human P450 1A1 and 1B1 differ in their stereospecific activation of DB[a,l]P. Mol. Carcinog. 26:74-82, 1999. Published 1999 Wiley-Liss, Inc.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0899-1987
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
74-82
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10506751-Animals, pubmed-meshheading:10506751-Benzopyrenes, pubmed-meshheading:10506751-Biotransformation, pubmed-meshheading:10506751-Carcinogens, pubmed-meshheading:10506751-Cattle, pubmed-meshheading:10506751-Cell-Free System, pubmed-meshheading:10506751-Chromatography, High Pressure Liquid, pubmed-meshheading:10506751-Chromatography, Thin Layer, pubmed-meshheading:10506751-Cytochrome P-450 Enzyme System, pubmed-meshheading:10506751-DNA, Complementary, pubmed-meshheading:10506751-DNA Adducts, pubmed-meshheading:10506751-Epoxide Hydrolases, pubmed-meshheading:10506751-Humans, pubmed-meshheading:10506751-Kinetics, pubmed-meshheading:10506751-Microsomes, pubmed-meshheading:10506751-Protein Isoforms, pubmed-meshheading:10506751-Recombinant Proteins, pubmed-meshheading:10506751-Thymus Gland, pubmed-meshheading:10506751-Time Factors
pubmed:year
1999
pubmed:articleTitle
A quantitative comparison of dibenzo[a,l]pyrene-DNA adduct formation by recombinant human cytochrome P450 microsomes.
pubmed:affiliation
Biochemistry and Pathobiology Branch, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
pubmed:publicationType
Journal Article, Comparative Study