Hydrochlorothiazide EnhancesUVA‐InducedDNADamage

AbstractTheUVAis currently thought to be carcinogenic because, similar toUVB, 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 generatedviaUV‐irradiated drugs play important roles in the pathogenesis of photosensitive drug eruptions. The waveband of concern for photo‐reactive drugs isUVA‐visible light, but some extend into theUVBregion. We tested whether photosensitive drugs could enhanceCPDformation afterUVAexposure by using isolatedDNAin the presence of several reported photosensitive drugs using high‐performance liquid chromatography. We found that the diuretic agent hydrochlorothiazide (HCT) significantly enhanced the production ofTTdimers over a wide range ofUVA. Furthermore, we investigated whetherUVAplusHCTcould enhanceCPDproduction in xeroderma pigmentosum model mice defective in nucleotide excision repair. Immunofluorescence studies showed thatCPDformation in the skin significantly increased after 365 nm narrow‐bandUVAirradiation in the presence ofHCT, compared with that in wild‐type mice.HCTcould be used with caution because of its enhancement ofUVA‐inducedDNAdamage.