Linked Life Data

14695185

Source:http://linkedlifedata.com/resource/pubmed/id/14695185

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2003-12-25
pubmed:abstractText
We investigated the effects of single and combined exposures to two ubiquitous environmental carcinogens, polycyclic aromatic hydrocarbons and UVA radiation, in Big Blue mouse embryonic fibroblasts. We quantified the cytotoxicity, DNA adduct formation, and induction of mutations in the cII transgene in cells treated with a single agent or combinations of agents in both direct and reverse order. Mapping of DNA adducts by terminal transferase-dependent PCR showed the preferential formation of bulky adducts at identical nucleotide positions along the cII gene after treatment with the prototype polycyclic aromatic hydrocarbon, benzo(a)pyrene diol epoxide [B(a)PDE], or B(a)PDE plus UVA radiation treatments but not after UVA irradiation alone. The cII mutant frequency determined by a lambda phage-based mutation detection system was not increased significantly by UVA irradiation (1.7-fold over background; P < 0.3); however, B(a)PDE alone or in combinations with UVA radiation significantly increased the cII mutant frequency (P < 0.001). The highest cII mutant frequency was induced by the treatment with B(a)PDE followed by UVA irradiation, which was more than the added mutant frequencies of the two agents individually (>12.2-fold versus <7.6-fold over background; P < 0.01). In support of these findings, DNA sequencing analyses showed that the mutational spectra induced by B(a)PDE alone or combined with UVA radiation were significantly different from those derived spontaneously (P < 0.0001) or by UVA irradiation (P < 0.0005). The signature of mutations produced by B(a)PDE i.e., "G-->T + C-->A" transversions, was significantly enhanced when the B(a)PDE treatment was followed by UVA irradiation (47% versus 65%; P < 0.01). Also, the methylated CpG dinucleotide-targeted overall mutations specifically induced by B(a)PDE were increased after the subsequent UVA irradiation (43% versus 51%, respectively). Such enhancements in the mutational signature of B(a)PDE were most pronounced within the preferential DNA adduction sites along the cII gene after the treatment with B(a)PDE plus UVA radiation, which suggests that the primary B(a)PDE adducts are converted to more mutagenic species on UVA irradiation. We conclude that UVA radiation at a nonmutagenic dose has an enhancing effect on the mechanism by which B(a)PDE induces mutations.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8708-16
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Enhancement of the mutagenicity of benzo(a)pyrene diol epoxide by a nonmutagenic dose of ultraviolet A radiation.
pubmed:affiliation
Division of Biology, Beckman Research Institute of the City of Hope National Medical Center, Duarte, California 91010-3000, USA. ania@coh.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.