抗菌药物监测报告显示，氢氯噻嗪（HCT）与皮肤癌有关，导致了治疗高血压和心力衰竭的HCT处方数量显著减少。HCT是否具有光毒性的性质，从而导致皮肤癌仍然未知。本研究旨在通过一项随机、安慰剂对照、双盲试验，对HCT在体内和体外的光敏化、光毒性和致癌潜力进行研究。该试验将30名健康、正常血压的成年志愿者按2：1比例分组，分别接受每天25mg的HCT或安慰剂治疗，持续15天。评估了HCT治疗对皮肤的光敏感性的影响。评估了全身紫外线A（UVA）和B（UVB，311nm）照射后通过测量嘧啶二聚体在尿液中的排泄来评估光毒性和致癌反应。对于体外研究，使用人体角质形成细胞（HaCaT）孵育HCT，然后用UVB照射，并分析其对炎症、凋亡和致癌的标志物的影响。暴露于UVA和UVB后的皮肤光敏感性在基线到15天的随访中两组均没有变化（UVA改变HCT 0.0 J/cm2 vs.安慰剂 0.0 J/cm2；P=0.99；UVB改变HCT 0.0 J/cm2 vs.安慰剂-0.2 J/cm2；P=0.06）。两组中均未检测到嘧啶二聚体。体外实验中，HCT和UVB照射的组合未诱导氧化应激标志蛋白、炎症蛋白、凋亡蛋白表达或致癌蛋白的激活。与安慰剂相比，HCT未增加健康志愿者对UVA或UVB的光敏感性，也未与光毒性或致癌反应相关联。在体外研究中，HCT也未与光毒性或致癌相关联（NCT04654312）。版权所有©2023 Wolters Kluwer Health，Inc. 保留所有权利。

Pharmocovigillance reports, associating hydrochlorothiazide (HCT) with skin cancer, resulted in a significant decrease of HCT prescriptions for hypertension and heart failure. Whether HCT exhibits phototoxic properties thereby causing skin cancer remains unknown. This study aimed to examine the photosensitizing, phototoxic and carcinogenic potential of HCT in a randomized, placebo-controlled, double-blinded trial in vivo and also in vitro.The trial assigned 30 healthy, normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg/day or placebo for 15 days. Photosensitivity of the skin with and without the effect of HCT treatment were assessed. Following whole-body ultraviolet A (UVA) and B (UVB, 311 nm) irradiation, phototoxic and carcinogenic reactions by measuring urinary excretion of pyrimidine dimers were evaluated. For the in-vitro studies, human keratinocytes (HaCaT) were incubated with HCT, irradiated with UVB, and analysed for markers of inflammation, apoptosis and carcinogenesis.Skin photosensitivity following exposure to UVA and UVB remained unchanged from baseline to 15-day follow-up in both groups (UVA change HCT 0.0 J/cm2 vs. placebo 0.0 J/cm2; P = 0.99; UVB change HCT 0.0 J/cm2 vs. placebo -0.2 J/cm2; P = 0.06). Pyrimidine dimers were not detected in either group. In vitro, combination of HCT and UVB irradiation did not induce the expression of oxidative stress marker proteins, inflammatory proteins, apoptotic proteins or activation of oncoproteins.HCT did not increase photosensitivity for UVA or UVB in healthy volunteers compared with placebo, and was not associated with phototoxic or carcinogenic reactions. In vitro, HCT was also not associated with phototoxicity or carcinogenesis (NCT04654312).Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.