Cyclobutane Pyrimidine Dimer Density as a Predictive Biomarker of the Biological Effects of Ultraviolet Radiation in Normal Human Fibroblast |
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| Authors: | Christopher D. Sproul David L. Mitchell Shangbang Rao Joseph G. Ibrahim William K. Kaufmann Marila Cordeiro‐Stone |
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| Affiliation: | 1. Curriculum in Toxicology, University of North Carolina at Chapel Hill, , Chapel Hill, NC;2. The University of Texas MD Anderson Cancer Center, Science Park/Research Division, University of North Carolina at Chapel Hill, , Chapel Hill, NC;3. Department of Biostatistics, University of North Carolina at Chapel Hill, , Chapel Hill, NC;4. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, , Chapel Hill, NC;5. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, , Chapel Hill, NC;6. Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, , Chapel Hill, NC |
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| Abstract: | This study compared biological responses of normal human fibroblasts (NHF1) to three sources of ultraviolet radiation (UVR), emitting UVC wavelengths, UVB wavelengths, or a combination of UVA and UVB (solar simulator; emission spectrum, 94.3% UVA and 5.7% UVB). The endpoints measured were cytotoxicity, intra‐S checkpoint activation, inhibition of DNA replication and mutagenicity. Results show that the magnitude of each response to the indicated radiation sources was best predicted by the density of DNA cyclobutane pyrimidine dimers (CPD). The density of 6‐4 pyrimidine–pyrimidone photoproducts was highest in DNA from UVC‐irradiated cells (14% of CPD) as compared to those exposed to UVB (11%) or UVA–UVB (7%). The solar simulator source, under the experimental conditions described here, did not induce the formation of 8‐oxo‐7,8‐dihydroguanine in NHF1 above background levels. Taken together, these results suggest that CPD play a dominant role in DNA damage responses and highlight the importance of using endogenous biomarkers to compare and report biological effects induced by different sources of UVR. |
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