Premium
Hydrochlorothiazide Enhances UVA ‐Induced DNA Damage
Author(s) -
Kunisada Makoto,
Masaki Taro,
Ono Ryusuke,
Morinaga Hironobu,
Nakano Eiji,
Yogianti Flandiana,
Okunishi Kunihiro,
Sugiyama Hiroshi,
Nishigori Chikako
Publication year - 2013
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12048
Subject(s) - hydrochlorothiazide , chemistry , dna damage , pyrimidine dimer , xeroderma pigmentosum , radical , drug , photosensitivity , carcinogen , dna , pharmacology , biophysics , biochemistry , medicine , biology , physics , quantum mechanics , blood pressure , radiology
The UVA is currently thought to be carcinogenic because, similar to UVB , it induces the formation of cyclobutane pyrimidine dimers ( CPD s). Various drugs have been reported to cause photosensitive drug eruptions as an adverse effect. Although the precise mechanism of photosensitive drug eruption remains to be elucidated, it is generally accepted that free radicals and other reactive molecules generated via UV ‐irradiated drugs play important roles in the pathogenesis of photosensitive drug eruptions. The waveband of concern for photo‐reactive drugs is UVA ‐visible light, but some extend into the UVB region. We tested whether photosensitive drugs could enhance CPD formation after UVA exposure by using isolated DNA in the presence of several reported photosensitive drugs using high‐performance liquid chromatography. We found that the diuretic agent hydrochlorothiazide ( HCT ) significantly enhanced the production of TT dimers over a wide range of UVA . Furthermore, we investigated whether UVA plus HCT could enhance CPD production in xeroderma pigmentosum model mice defective in nucleotide excision repair. Immunofluorescence studies showed that CPD formation in the skin significantly increased after 365 nm narrow‐band UVA irradiation in the presence of HCT , compared with that in wild‐type mice. HCT could be used with caution because of its enhancement of UVA ‐induced DNA damage.