title: Hydrochlorothiazide enhances UVA-induced DNA damage.
abstract: The UVA is currently thought to be carcinogenic because, similar to UVB, it induces the formation of cyclobutane pyrimidine dimers (CPDs). 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.
authors: Division of Dermatology, Department of Internal Related Graduate School of Medicine, Kobe University, Kobe, Japan.
authors: Makoto
authors: M
authors: Kunisada
authors: Taro
authors: T
authors: Masaki
authors: Ryusuke
authors: R
authors: Ono
authors: Hironobu
authors: H
authors: Morinaga
authors: Eiji
authors: E
authors: Nakano
authors: Flandiana
authors: F
authors: Yogianti
authors: Kunihiro
authors: K
authors: Okunishi
authors: Hiroshi
authors: H
authors: Sugiyama
authors: Chikako
authors: C
authors: Nishigori
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004195:Disease Models, Animal; D004232:Diuretics / Q000009:adverse effects* / Q000737:chemistry; D006852:Hydrochlorothiazide / Q000009:adverse effects* / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D017319:Photosensitizing Agents / Q000009:adverse effects* / Q000737:chemistry; D011740:Pyrimidine Dimers / Q000096:biosynthesis* / Q000737:chemistry; D012867:Skin / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D014983:Xeroderma Pigmentosum / Q000737:chemistry* / Q000235:genetics / Q000473:pathology
chemical_list: D004232:Diuretics; D017319:Photosensitizing Agents; D011740:Pyrimidine Dimers; D006852:Hydrochlorothiazide; D004247:DNA