Linked Life Data

15492252

Source:http://linkedlifedata.com/resource/pubmed/id/15492252

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2004-10-19
pubmed:abstractText
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens. PAHs are classified into bay and fjord region compounds according to structural differences in the molecule region where enzymatic epoxidation occurs. Dibenzo[a,l]pyrene (DB[a,l]P), one of the fjord region compounds, has been demonstrated to be the most carcinogenic PAH known to date. DB[a,l]P is activated to fjord region (+)-syn and (-)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) metabolites. In this study, we analyzed mutagenesis induced by (+)-syn- and (-)-anti-DB[a,l]PDE at the cII transgene in Big-Blue mouse cells. The mutant frequency of untreated cells (background level) was 6.53 x 10(-5). This level increased 3.7-fold for 20 nmol/L, 5.3-fold for 50 nmol/L, and 7.9-fold for 100 nmol/L (+)-syn-DB[a,l]PDE, respectively. In the case of (-)-anti-DB[a,l]PDE it increased 4.5-fold for 20 nmol/L, 6.7-fold for 50 nmol/L, and 10.6-fold for 100 nmol/L, respectively, indicating that (-)-anti-DB[a,l]PDE is slightly more mutagenic than (+)-syn-DB[a,l]PDE. The mutational spectra of (+)-syn- and (-)-anti-DB[a,l]PDE were quite similar except for several hotspots, specific for either (+)-syn-DB[a,l]PDE or (-)-anti-DB[a,l]PDE. The most frequently induced mutations were A to T transversions, which were 43.9% for (+)-syn- and 38.8% for (-)-anti-DB[a,l]PDE. In addition, G to T transversions were induced significantly, at frequencies of 18.5% by (+)-syn- and 18.1% by (-)-anti-DB[a,l]PDE. Using UvrABC cleavage and ligation-mediated PCR or the terminal transferase-dependent PCR method, we have determined DB[a,l]PDE-DNA adduct formation sites and repair rates in carcinogen-exposed cells. The mutation hotspots coincided with sites of strong adduct formation, but not all of the adduct hotspots were mutational hotspots. Slow adduct removal occurred for both (+)-syn- and (-)-anti-DB[a,l]PDE adducts over a time period of up to 72 hours. The data suggest that, although the (-)-anti-isomer is slightly more mutagenic, DNA adducts of both DB[a,l]PDE stereoisomers may have similar biological properties. We discuss the implications of these findings for human cancer mutagenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7321-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15492252-Animals, pubmed-meshheading:15492252-Base Sequence, pubmed-meshheading:15492252-Benzopyrenes, pubmed-meshheading:15492252-Chromosome Mapping, pubmed-meshheading:15492252-DNA Adducts, pubmed-meshheading:15492252-DNA Damage, pubmed-meshheading:15492252-DNA Repair, pubmed-meshheading:15492252-Embryo, Mammalian, pubmed-meshheading:15492252-Epoxy Compounds, pubmed-meshheading:15492252-Fibroblasts, pubmed-meshheading:15492252-Mice, pubmed-meshheading:15492252-Mice, Transgenic, pubmed-meshheading:15492252-Molecular Sequence Data, pubmed-meshheading:15492252-Mutagenesis, pubmed-meshheading:15492252-Mutagens, pubmed-meshheading:15492252-Polymerase Chain Reaction, pubmed-meshheading:15492252-Stereoisomerism, pubmed-meshheading:15492252-Transcription Factors, pubmed-meshheading:15492252-Transgenes, pubmed-meshheading:15492252-Viral Proteins
pubmed:year
2004
pubmed:articleTitle
DNA damage, repair, and mutation induction by (+)-Syn and (-)-anti-dibenzo[a,l]pyrene-11,12-diol-13,14-epoxides in mouse cells.
pubmed:affiliation
Beckman Research Institute of the City of Hope, Duarte, California, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.