Enhancing DNA repair in the skin: A pilot study of low-dose chloroquine and ultraviolet light.

Abstract

8566 Background: Inability to repair ultraviolet light (UV)-induced DNA damage causes skin cancer. Chloroquine has been shown to activate the DNA damage response pathway. The aim of this pilot study is to determine the potential role of chloroquine in skin cancer chemoprevention through upregulation of DNA damage repair pathways. Methods: Thirty subjects aged 23-60 years with fair skin were enrolled. Each subject was given chloroquine 500 mg per week for 4 weeks. The minimal erythema dose (MED) of artificial UV light was determined for each subject, and skin biopsies of MED sites (24 hours after UV exposure) were obtained before and after chloroquine therapy. DNA damage was assessed using immunohistochemical detection of thymine dimers; activation of p53 was assessed by detection of its downstream target p21. Image analysis was performed with Aperio Digital Pathology software. Our hypothesis is that chloroquine upregulates DNA repair pathways prior to UV irradiation leading to increased repair of UV-induced DNA damage. Twenty-four hours after UV irradiation we expect to observe less DNA damage and lower p21 levels in skin biopsies after chloroquine treatment than before treatment. Results: Fifteen of 30 subjects showed an increase in MED, indicating decreased sensitivity to UV light after chloroquine treatment. Six subjects had MED increases of 200 mj/cm2 and 9 had increases of 100 mj/cm2. Fourteen subjects showed no change in MED and 1 subject had a decrease in MED by 100 mj/cm2. Preliminary immunohistochemical analyses for thymine dimers and p21 expression demonstrate consistency with respect to the response to chloroquine in 82% of subjects. Decreased thymine dimers, decreased p21 levels and/or increased MED was observed in 55% of subjects. Increased dimers, increased p21 and/or no change in MED was observed in 27% of subjects. Discordant results were observed in 18% of subjects. Conclusions: Chloroquine can exert a measurable photoprotective response in human skin. It may also upregulate DNA damage repair pathways leading to decreased DNA damage after UV exposure. These results may lead to further studies regarding the role of chloroquine and similar drugs in the repair of DNA damage and the prevention of skin cancers. No significant financial relationships to disclose.