Azathioprine treatment photosensitizes human skin to ultraviolet A radiation.
BACKGROUND
Azathioprine is used to treat a variety of conditions and to prevent graft rejection in organ transplant recipients (OTRs).


OBJECTIVE
To investigate clinically our previous finding that azathioprine metabolites interact with ultraviolet (UV) A radiation to form promutagenic oxidative DNA damage and to determine whether this may be causal or contributory to the development of excess skin cancers post-transplantation.


METHODS
The clinical corollary of these data were investigated. Five patients were recruited and the minimal erythema dose (MED) for UVB, UVA and solar-simulated radiation (SSR) was determined for each person before, and at least 12 weeks after, starting azathioprine therapy.


RESULTS
In all five patients azathioprine treatment was associated with an increased UVA and SSR sensitivity of the skin and a significant reduction in MEDs for UVA and SSR. We found no change in UVB-induced erythema or MED. In addition, we found that DNA from the skin of patients on azathioprine contains 6-thioguanine (6-TG).


CONCLUSIONS
Our findings confirm the presence of DNA 6-TG in the skin of those taking therapeutic doses of azathioprine and provide support for the hypothesis that DNA damage occurs when DNA 6-TG interacts with UVA, resulting in abnormal cutaneous photosensitivity.
Perrett
C M
CM
Centre for Cutaneous Research and Department of Dermatology, Institute of Cell and Molecular Science, Barts and The London, Queen Mary School of Medicine and Dentistry, 4 Newark Street, London, E1 2AT, UK. conalperrett@hotmail.com
Walker
S L
SL
O'Donovan
P
P
Warwick
J
J
Harwood
C A
CA
Karran
P
P
McGregor
J M
JM
D000328:Adult; D001379:Azathioprine / Q000009:adverse effects*; D016022:Case-Control Studies; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004817:Epidermis / Q000528:radiation effects; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010787:Photosensitivity Disorders / Q000139:chemically induced*; D012878:Skin Neoplasms / Q000209:etiology*; D013866:Thioguanine / Q000009:adverse effects; D016896:Treatment Outcome; D014467:Ultraviolet Therapy / Q000009:adverse effects*
D007166:Immunosuppressive Agents; D013866:Thioguanine; D001379:Azathioprine