Hydrochlorothiazide enhances UVA-induced DNA damage

Area of Science:

• Photobiology
• Dermatology
• Molecular Biology

Background:

• UVA radiation is carcinogenic, inducing DNA damage like cyclobutane pyrimidine dimers (CPDs).
• Photosensitive drug eruptions are linked to UV-irradiated drugs generating reactive molecules.
• The role of specific drugs in enhancing UV-induced DNA damage requires further investigation.

Purpose of the Study:

• To investigate whether photosensitive drugs enhance CPD formation following UVA exposure.
• To determine the specific effect of hydrochlorothiazide (HCT) on UVA-induced DNA damage.
• To evaluate the in vivo effect of UVA and HCT on DNA damage in a mouse model.

Main Methods:

• High-performance liquid chromatography (HPLC) was used to quantify CPDs in isolated DNA exposed to UVA and photosensitive drugs.
• Immunofluorescence studies were conducted on xeroderma pigmentosum model mice (defective in nucleotide excision repair) and wild-type mice.
• Mice were irradiated with 365 nm narrow-band UVA in the presence or absence of HCT.

Main Results:

• Hydrochlorothiazide (HCT) significantly enhanced the formation of thymine-thymine (TT) dimers in isolated DNA across a range of UVA wavelengths.
• In vivo studies showed significantly increased CPD formation in the skin of mice exposed to UVA and HCT compared to controls.
• Xeroderma pigmentosum model mice exhibited enhanced CPD formation, indicating a role for DNA repair mechanisms.

Conclusions:

• Hydrochlorothiazide (HCT) demonstrably enhances UVA-induced DNA damage, specifically CPD formation.
• The findings suggest that HCT may increase susceptibility to UV-related skin damage.
• Caution is advised when using hydrochlorothiazide due to its potential to augment UVA-induced DNA damage.