UVA photoactivation of DNA containing halogenated thiopyrimidines induces cytotoxic DNA lesions

Journal of Photochemistry and Photobiology. B, Biology
Reto BremPeter Karran

Abstract

Photochemotherapy, the combination of a photosensitiser and ultraviolet (UV) or visible light, is an effective treatment for skin conditions including cancer. The high mutagenicity and non-selectivity of photochemotherapy regimes warrants the development of alternative approaches. We demonstrate that the thiopyrimidine nucleosides 5-bromo-4-thiodeoxyuridine (SBrdU) and 5-iodo-4-thiodeoxyuridine (SIdU) are incorporated into the DNA of cultured human and mouse cells where they synergistically sensitise killing by low doses of UVA radiation. The DNA halothiopyrimidine/UVA combinations induce DNA interstrand crosslinks, DNA-protein crosslinks, DNA strand breaks, nucleobase damage and lesions that resemble UV-induced pyrimidine(6-4)pyrimidone photoproducts. These are potentially lethal DNA lesions and cells defective in their repair are hypersensitive to killing by SBrdU/UVA and SIdU/UVA. DNA SIdU and SBrdU generate lethal DNA photodamage by partially distinct mechanisms that reflect the different photolabilities of their C-I and C-Br bonds. Although singlet oxygen is involved in photolesion formation, DNA SBrdU and SIdU photoactivation does not detectably increase DNA 8-oxoguanine levels. The absence of significant collateral damag...Continue Reading

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Citations

Jun 22, 2016·DNA Repair·Peter Karran, Reto Brem
Apr 27, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daiva TauraitėRolandas Meškys
Oct 19, 2016·Magnetic Resonance in Chemistry : MRC·Xiao-Hui Zhang, Yao-Zhong Xu
Oct 7, 2015·Physical Chemistry Chemical Physics : PCCP·M PollumC E Crespo-Hernández
May 31, 2017·Radiation Research·Mohammad RezaeeDavid A Jaffray
Mar 14, 2018·ChemMedChem·Marvin PollumCarlos E Crespo-Hernández
Jul 7, 2018·Photochemistry and Photobiology·Brennan AshwoodCarlos E Crespo-Hernández
Mar 17, 2019·International Journal of Molecular Sciences·Samanta MakuratMagdalena Zdrowowicz
Dec 8, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Konrad SkotnickiKrzysztof Bobrowski
Aug 7, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paulina SpiszJanusz Rak
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paweł WitykRobert Nowak

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Methods Mentioned

BETA
electrophoresis
ELISA

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