The Use of Specific Radioimmunoassays to Determine Action Spectra for the Photolysis of (6‐4) Photoproducts

Mitchell, David L.; Rosenstein, Barry S.

doi:10.1111/j.1751-1097.1987.tb07882.x

Cited by 66 publications

(35 citation statements)

References 15 publications

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“…The second most numerous class are pyrimidine(6-4)pyrimidones. Although the biological significance of pyrimidine(6-4)pyrimidone photoproducts vis-a-vis pyrimidine dimers is not yet clear, the action spectrum for the formation of pyrimidine(6-4)pyrimidone photoproducts is almost identical to that for dimers asjudged both by direct chemical assay (29) and by RIA (30) when allowance is made for the subsequent photolysis of the pyrimidine(6-4)pyrimidone photoproducts (31). Thus, the calculations of the relative increases in DNA damage resulting from decreased stratospheric ozone apply to the biological consequences of both pyrimidine(6-4)pyrimidone photoproducts and pyrimidine dimers.…”

Section: Discussionmentioning

confidence: 99%

Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light.

Freeman

Hacham

Gange

et al. 1989

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

287

172

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The UV components of sunlight are believed to be a major cause of human skin cancer, and DNA is thought to be the principal molecular target. Alterations of the intensity and wavelength distribution of solar UV radiation reaching the surface of the earth, for example by depletion of stratospheric ozone, will change the effectiveness of solar radiation in damaging DNA in human skin. Evaluation of the magnitude of such effects requires knowledge of the altered sunlight spectrum and of the action spectrum for damaging DNA in human skin. We have determined an action spectrum for the frequency of pyrimidine dimer formation induced in the DNA of human skin per unit dose of UV incident on the skin surface. The peak of this action spectrum is near 300 nm and decreases rapidly at both longer and shorter wavelengths. The decrease in our action spectrum for wavelengths <300 nm is attributed to the absorption of the upper layers of the skin, an in situ effect that is inherently included in our measurements. Convolution of the dimer action spectrum with the solar spectra corresponding to a solar angle of 40' under current levels of stratospheric ozone (0.32-cm 03 layer) and those for 50% ozone depletion (0.16-cm 03 layer), indicate about a 2.5-fold increase in dimer formation. If the action spectrum for DNA damage that results in skin cancer resembles that for dimer induction in skin, our results, combined with epidemiological data, suggest that a 50% decrease in stratospheric ozone would increase the incidence of nonmelanoma skin cancers among white males in Seattle, Washington, by 7.5-to 8-fold, to a higher incidence than is presently seen in the corresponding population of Albuquerque, New Mexico.Sunlight causes erythema, premature aging, and cancers in human skin (1), and several lines ofevidence indicate that UV radiation of wavelengths <320 nm is of primary importance in damage induction (2). Studies of the wavelength dependence of carcinogenesis in mouse skin (3) and of erythema induction in human skin (4) indicate that the efficiency of damage induction by photons in the wavelength range 290-400 nm varies strikingly. Thus, alteration of the solar spectrum reaching the earth's surface-for example, through alteration in the ozone content of the stratosphere-will affect the frequency of DNA damages, including those in human skin.Quantitative prediction of the extent of damage and of its biological consequences requires convolution of the altered solar spectrum with the action spectrum for inducing human skin cancer (2). Because this action spectrum is not known, other biological response functions have been used to approximate the human skin cancer spectrum: action spectra (i) for carcinogenesis in mouse skin (3), (ii) for killing and mutation in prokaryotes (2), and (iii) for killing, mutation, and transformation of mammalian cells in culture (5, 6), as well as several different action spectra (iv) for erythema in human skin (4, 7). However, the optical properties of mouse skin and of prokaryotes and mammalian ...

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Section: Discussionmentioning

confidence: 99%

Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light.

Freeman

Hacham

Gange

et al. 1989

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

287

172

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“…92.' 19 Transversions largely predominate, and GC -AT transitions represent only 15% of the mutations. As previously observed for other systems, most mutations occur at bipyrimidines, and tandem double changes are also recovered.…”

Section: At Endogenous Loci In Mammalian Cells Uvc-inducedmentioning

confidence: 99%

Distribution and Repair of Photolesions in Dna: Genetic Consequences and the Role of Sequence Context

Sage

1993

Photochem & Photobiology

226

108

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“…A second DNA repair system, namely the Escherichia coli Uvr ABC complex, has been used in combination with a photolyase for the quantitation of cyclobutane dimers and (6-4) photoproducts (14). Another widely applied biochemical approach involves the use of either polyclonal or monoclonal antibodies able to recognize specific classes of pyrimidine photoproducts (15)(16)(17)(18)(19)(20)(21)(22). However, most of the immunological assays suffer from a lack of calibration.…”

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confidence: 99%

Formation of the Main UV-induced Thymine Dimeric Lesions within Isolated and Cellular DNA as Measured by High Performance Liquid Chromatography-Tandem Mass Spectrometry

Douki¹,

Court²,

Sauvaigo³

et al. 2000

Journal of Biological Chemistry

227

194

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UVB radiation-induced formation of dimeric photoproducts at bipyrimidine sites within DNA has been unambiguously associated with the lethal and mutagenic properties of sunlight. The main lesions include the cyclobutane pyrimidine dimers and the pyrimidine (6-4) pyrimidone adducts. The latter compounds have been shown in model systems to be converted into their Dewar valence isomers upon exposure to UVB light. A new direct assay, based on the use of liquid chromatography coupled to tandem mass spectrometry, is now available to simultaneously detect each of the thymine photoproducts. It was applied to the determination of the yields of formation of the thymine lesions within both isolated and cellular DNA exposed to either UVC or UVB radiation. The cis-syn cyclobutane thymine dimer was found to be the major photoproduct within cellular DNA, whereas the related (6-4) adduct was produced in an approximately 8-fold lower yield. Interestingly, the corresponding Dewar valence isomer could not be detected upon exposure of human cells to biologically relevant doses of UVB radiation.Ultraviolet radiation represents the most deleterious part of solar light to cells and has been associated with the occurrence of skin cancer (1). UVB (290 -320 nm) radiation is highly mutagenic (2, 3) and mostly induces mutations at bipyrimidine sites in cellular DNA (4 -7). Interestingly, a similar mutation spectrum was observed in the p53 gene of skin tumors cells (8,9). Altogether, these data outlined the biological role of dimeric photoproducts of pyrimidine DNA bases. In the last four decades, major efforts have been devoted to the isolation and the characterization of bipyrimidine photolesions in model compounds and isolated DNA (for reviews, see Refs. 10 and 11). These include the cis-syn and trans-syn diastereoisomers of cyclobutane dimers and the pyrimidine (6-4) pyrimidone adducts (Fig. 1). The latter lesions have been shown to undergo an efficient photoconversion into their Dewar valence isomers upon exposure to UVB light (12).Information on the rate of formation of each specific photoproduct is still needed. Indeed, most of the assays developed for the detection of UV-induced photoproducts within DNA involve the use of indirect methods that do not allow differentiation, for a given class of photoproduct, of the lesions arising from the different possible bipyrimidinic sequences. Cyclobutane pyrimidine dimers have been extensively detected by using T4 endonuclease V, which exhibits a N-glycosylase activity at the 5Ј-extremity of the lesion (13). This leads to the formation of strand breaks, which can be quantified using electrophoretic techniques. A second DNA repair system, namely the Escherichia coli Uvr ABC complex, has been used in combination with a photolyase for the quantitation of cyclobutane dimers and (6-4) photoproducts (14). Another widely applied biochemical approach involves the use of either polyclonal or monoclonal antibodies able to recognize specific classes of pyrimidine photoproducts (15)(16)(17)(18)(19)(20)(21)...

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The Use of Specific Radioimmunoassays to Determine Action Spectra for the Photolysis of (6‐4) Photoproducts

Cited by 66 publications

References 15 publications

Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light.

Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light.

Distribution and Repair of Photolesions in Dna: Genetic Consequences and the Role of Sequence Context

Formation of the Main UV-induced Thymine Dimeric Lesions within Isolated and Cellular DNA as Measured by High Performance Liquid Chromatography-Tandem Mass Spectrometry

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