Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-12-21
pubmed:abstractText
Psoriatic patients undergoing psoralen plus ultraviolet radiation (PUVA) therapy are susceptible for squamous cell carcinoma and melanoma of the skin. To investigate the etiological relevance of PUVA for these diseases, we performed mutation spectrometry on the cII transgene in mouse embryonic fibroblasts treated with a single or split PUVA dose (PUVA-I or PUVA-II, respectively). Both treatments were significantly mutagenic as they increased the cII mutant frequency up to 3.7-fold over background, and produced different mutational spectra from that derived spontaneously (p<0.01), but not from one another. The signature of induced mutations, i.e., T to C transitions and T to A transversions with significant site-specificities, i.e., adjacent to T bases at the 3'-neighboring side and to pyrimidines at the 5'-neighboring side, was more pronounced after PUVA-II treatment. Also, the overall mutations occurring at T bases with the same site-specificities were more prevalent after PUVA-II treatment. The characteristic PUVA-induced mutations predominate in the p53 mutational spectrum in controlled in vivo test systems or in high-dose PUVA-treated patients, and also are easily recognizable in the overall PUVA-treated patients. We conclude that PUVA-induced mutagenesis is initiated by PUVA-I treatment and subsequently, augmented by PUVA-II treatment, leaving a unique mutational signature on the cII transgene. The signature mutations of PUVA are discernible in the p53 mutational spectrum in PUVA-treated patients but complex exposure to other therapeutic/environmental carcinogens also leads to the frequent occurrence of other types of mutations in this population.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-202X
pubmed:author
pubmed:issnType
Print
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1140-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Biological consequences of 8-methoxypsoralen-photoinduced lesions: sequence-specificity of mutations and preponderance of T to C and T to a mutations.
pubmed:affiliation
Division of Biology, Beckman Research Institute of the City of Hope National Medical Center, Duarte, California, USA. ania@coh.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.