Azathioprine treatment photosensitizes human skin to ultraviolet A radiation

Authors

  • C.M. Perrett,

    1. 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, U.K.
    2. Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, U.K.
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  • S.L. Walker,

    1. Department of Environmental Photobiology, St John’s Institute of Dermatology, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • P. O’Donovan,

    1. Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, U.K.
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  • J. Warwick,

    1. Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, U.K.
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  • C.A. Harwood,

    1. 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, U.K.
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  • P. Karran,

    1. Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, U.K.
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  • J.M. McGregor

    1. 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, U.K.
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  • Conflicts of interest None declared.

C.M. Perrett.
E-mail:conalperrett@hotmail.com

Summary

Background  Azathioprine is used to treat a variety of conditions and to prevent graft rejection in organ transplant recipients (OTRs).

Objectives  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.

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