Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well established that exposure to solar UVB (290-320 nm) gives rise to mutations in oncogenes and tumor suppressor genes that initiate the molecular cascade toward skin cancer. Although UVA (320-400 nm) has also been implicated in multistage photocarcinogenesis, its potential contribution to sunlight mutagenesis remains poorly characterized. We have determined the DNA sequence specificity of mutations induced by UVB (lambda > 290 nm), and by UVA (lambda > 350 nm), at the adenine phosphoribosyltransferase locus of Chinese hamster ovary cells. This has been compared to results previously obtained for stimulated sunlight (lambda > or = 310 nm) and 254-nm UVC in the same gene. We demonstrate that T-->G transversions, a generally rare class of mutation, are induced at high frequency (up to 50%) in UVA-exposed cells. Furthermore, this event comprises a substantial proportion of the simulated sunlight-induced mutant collection (25%) but is significantly less frequent (P < 0.05) in cells irradiated with either UVB (9%) or UVC (5%). We conclude that the mutagenic specificity of broad-spectrum solar light in rodent cells is not determined entirely by the UVB component and that UVA also plays an important role.
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PMID:A role for ultraviolet A in solar mutagenesis. 789 70

To investigate the role of nucleotide excision repair (NER) in the cellular processing of carcinogenic DNA photoproducts induced by defined, environmentally relevant portions of the solar wavelength spectrum, we have determined the mutagenic specificity of simulated sunlight (310-1100 nm), UVA (350-400 nm), and UVB (290-320 nm), as well as of the "nonsolar" model mutagen 254-nm UVC, at the adenine phosphoribosyltransferase (aprt) locus in NER-deficient (ERCC1) Chinese hamster ovary (CHO) cells. The frequency distributions of mutational classes induced by UVB and by simulated sunlight in repair-deficient CHO cells were virtually identical, each showing a marked increase in tandem CC-->TT transitions relative to NER-proficient cells. A striking increase in CC-->TT events was also previously documented for mutated p53 tumor-suppressor genes from nonmelanoma tumors of NER-deficient, skin cancer-prone xeroderma pigmentosum patients, compared to normal individuals. The data therefore indicate that the aprt gene in NER-deficient cultured rodent cells irradiated with artificial solar light generates the same distinctive "fingerprint" for sunlight mutagenesis as the p53 locus in NER-deficient humans exposed to natural sunlight in vivo. Moreover, in strong contrast to the situation for repair-component CHO cells, where a significant role for UVA was previously noted, the mutagenic specificity of simulated sunlight in NER-deficient CHO cells and of natural sunlight in humans afflicted with xeroderma pigmentosum can be entirely accounted for by the UVB portion of the solar wavelength spectrum.
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PMID:Mutagenic specificity of solar UV light in nucleotide excision repair-deficient rodent cells. 855 99