Determination of the Spectrum of Mutations Induced by Defined-Wavelength Solar UVB (313-nm) Radiation in Mammalian Cells by Use of a Shuttle Vector

Keyse, Stephen M.; Amaudruz, Francoise; Tyrrell, Rex M.

doi:10.1128/mcb.8.12.5425-5431.1988

Cited by 13 publications

(3 citation statements)

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“…The pattern and the distribution of mutations induced by 102 in supF gene are quite different from what has been reported for similar systems, on which mutations are due to DNA treatment by agents that generate other oxygen radicals (29,30).…”

Section: Discussioncontrasting

confidence: 77%

“…The types of mutation detected in these experiments are considerably different from the data obtained for spontaneous mutations in the supF gene of SV40-based shuttle vectors after passage through mammalian cells (28,29,30). Most of the independent mutants analysed (49 of 57) were obtained from Total 57 100.0 * only independent mutants were considered.…”

Section: Types Of 102-induced Mutationsmentioning

confidence: 71%

“…The presence of repair mechanims strengths the importance of these lesions. It should also be pointed out that multiple mutations are frequently observed in SV40-based shuttle vector mutagenesis reports (28,29,36). Thus, the presence of this kind of mutation may be a specific feature and a limitation of such vectors.…”

Section: Discussionmentioning

confidence: 99%

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Singlet Oxygen induced mutation spectrum in mammalian cells

et al. 1992

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In order to characterize the molecular nature of singlet oxygen (1O2) induced mutations in mammalian cells, a SV40-based shuttle vector (pi SVPC13) was treated with singlet oxygen arising from the thermal decomposition of the water-soluble endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2). After the passage of damaged plasmid through monkey COS7 cells, the vector was shuffled into E. coli cells, allowing the screening of supF mutants. The mutation spectrum analysis shows that single and multiple base substitutions arose in 82.5% of the mutants, the others being rearrangements. The distribution of mutations within the supF gene is not random and some hotspots are evident. Most of the point mutations (98.4%) involve G:C base pairs and G:C to T:A transversion was the most frequent mutation (50.8%), followed by G:C to C:G transversion (32.8%). These results indicate that mutagenesis in mammalian cells, mediated by 1O2-induced DNA damage, is targeted selectively at guanine residues.

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Section: Discussioncontrasting

confidence: 77%

Section: Types Of 102-induced Mutationsmentioning

confidence: 71%

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Singlet Oxygen induced mutation spectrum in mammalian cells

et al. 1992

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Mechanism of Abnormal Elastin Gene Expression in the Pinguecular Part of Pterygia

Wang

Chen

et al. 2000

The American Journal of Pathology

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Elastodysplasia and elastodystrophy are two known manifestations in the conjunctival, ie, pinguecular, part of pterygia. But the mechanisms are still not understood. The purpose of this study is to investigate the mechanism of enhanced elastin gene expression in fibroblasts from the pinguecular part of pterygia, which is related to abnormal elastic fiber expression in the pinguecular part of pterygia. Elastin in surgical specimens of normal conjunctiva and the pinguecular part of pterygia from age-matched patients was detected by immunohistochemical staining. Northern hybridization and quantification of radiolabeled tropoelastin were performed in conjunctival fibroblasts cultured under different doses of ultraviolet (UV) B irradiation, and in cultured pinguecular fibroblasts from pterygia. In vitro translation was also performed to analyze the tropoelastin production in rabbit reticulocyte lysate. The level of tropoelastin in reticulolysates from UV-treated conjunctival and pinguecular fibroblasts of pterygia was higher than in normal conjunctival fibroblasts. The coding sequence and 3'- untranslated region of tropoelastin mRNAs were amplified by reverse transcription-polymerase chain reaction, and mutations were checked by DNA sequencing. Immunohistochemical staining revealed elastin in pinguecular subepithelial connective tissues of pterygia, but not in normal conjunctiva. Tropoelastin mRNA levels were not elevated in cultured pinguecular or conjunctival fibroblasts with or without ultraviolet B irradiation. However, tropoelastin synthesis was enhanced in culture medium of pinguecular and UV-irradiated conjunctival fibroblasts, but not in normal conjunctival fibroblasts. Direct DNA sequencing revealed mutations in the 3'-untranslated region but not in the coding sequence of tropoelastin mRNA, in both pinguecular and UV-irradiated conjunctival fibroblasts. The increased expression of tropoelastin in pinguecular and UV-irradiated fibroblasts is not a result of increased levels of steady-state mRNA, but is a result of posttranscriptional modification of tropoelastin.

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Site and strand specificity of UVB mutagenesis in the SUP4-o gene of yeast.

Armstrong

Kunz

1990

Proc. Natl. Acad. Sci. U.S.A.

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DNA sequencing was used to characterize 208 mutations induced in the SUP4-o tRNA gene of the yeast Saceharomyces cerevisiae by UVB (285-320 am) radiation. The results were compared to those for an analysis of 211 SUP4-o mutations induced by 254-nm UVC light. In each case, >90% of the mutations were single base-pair changes but GC -+ APT transitions predominated and accounted for more of the mutations induced by UVB than UVC. Double substitutions, single base-pair deletions, and more complex events were also recovered. However, UVB induced 3-fold more tandem substitutions than UVC and nontandem double events were detected only after irradiation with UVC. Virtually all induced substitutions occurred at sites where the pyrimidine of the base pair was part of a dipyrimidine sequence. Although the site specificities were consistent with roles for cyclobutane dimers and pyrimidinepyrimidone(6-4) lesions in mutation induction, preliminary photoreactivation data implicated cyclobutane dimers as the major form of premutational DNA damage for both agents.Intriguingly, there was a preference for both UVB-and UVCinduced mutations to occur at sites where the dipyrimidine was on the transcribed strand.Exposure to sunlight has been linked with the development of human skin cancer and experimental evidence indicates that among the wavelengths that penetrate the ozone layer, those responsible for carcinogenesis are within the UVB (280-320 nm) region ofthe solar spectrum (1-3). Although the precise mechanism is unknown, DNA damage, as expressed by genetic mutation, is very likely to be involved in the induction of cancer by sunlight. Indeed, the human disorder xeroderma pigmentosum involves defective repair of UVinduced DNA lesions and sensitizes affected individuals to solar photocarcinogenesis (4). Furthermore, sunlight has been shown to mutagenize Chinese hamster cells (5) and UVB wavelengths are mutagenic to bacterial, yeast, and mammalian cells (6-8).It is generally considered that cyclobutane pyrimidine dimers and pyrimidine-pyrimidone(6-4) photoproducts [(6-4) photoproducts] are the most important premutational DNA lesions induced by UVC (200-280 nm) radiation (9, 10). Although UVB wavelengths also produce these two types of photoproduct (6,(10)(11)(12), other lesions such as DNA strand breaks and thymine glycols are induced by UVB treatment (13,14). The precise roles of these various lesions in UVB mutagenesis, and thus the mechanism(s) involved, have yet to be established. There is evidence implicating cyclobutane dimers and (6-4) photoproducts in the mutagenicity of UVB radiation (12, 15), but there also are indications that the nondimer lesions may contribute significantly (6, 15). To add to the complexity of this situation, other factors may influence the production of UVB-induced mutations. For exampie, UVC-induced cyclobutane dimers are selectively repaired in the transcribed strand of transcriptionally active dhfr, lacI, or URA3 genes in human and rodent, bacterial, or yeast cells, respectively (16)(17)(1...

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Determination of the Spectrum of Mutations Induced by Defined-Wavelength Solar UVB (313-nm) Radiation in Mammalian Cells by Use of a Shuttle Vector

Cited by 13 publications

References 27 publications

Singlet Oxygen induced mutation spectrum in mammalian cells

Singlet Oxygen induced mutation spectrum in mammalian cells

Mechanism of Abnormal Elastin Gene Expression in the Pinguecular Part of Pterygia

Site and strand specificity of UVB mutagenesis in the SUP4-o gene of yeast.

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