期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 12, 期 1, 页码 218-225出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1600-6143.2011.03751.x
关键词
Azathioprine; kidney transplantation; skin photosensitivity; UVA; 6-thioguanine DNA
资金
- Olga-Mayenfisch Foundation in Zurich, Switzerland
- EMDO Foundation in Zurich, Switzerland
- Hartmann-Muller-Foundation in Zurich, Switzerland
- University Medical Faculty Research Foundation in Zurich, Switzerland
- Hoffmann-LaRoche, Basel, Switzerland
- Cancer Research UK
- Hoffmann LaRoche AG, Basel, Switzerland
- manufacturer of MMF (CellCept(R))
- Cancer Research UK [13044, 11584] Funding Source: researchfish
Azathioprine is associated with enhanced skin photosensitivity to ultraviolet A (UVA) and leads to incorporation of 6-thioguanine (6-TG) into DNA of dividing cells. Unlike canonical DNA, 6-TG DNA is damaged by UVA, which comprises more than 90% of the ultraviolet reaching earth. Skin photosensitivity to UVA and UVB was measured in 48 kidney transplant patients immunosuppressed either by azathioprine (n = 32) or mycophenolate (n = 16). In 23 patients, azathioprine was subsequently replaced by mycophenolate and skin photosensitivity, DNA 6-TG content in peripheral blood mononuclear cells, and susceptibility to UVA-induced DNA damage were monitored for up to 2 years. The mean minimal erythema dose to UVA on azathioprine was twofold lower than on mycophenolate. Three months after replacing azathioprine by mycophenolate mofetil, the minimal erythema dose to UVA had increased from 15 to 25 J/cm2 (p < 0.001) accompanied by reduced DNA 6-TG content. P53 protein expression in irradiated skin indicated reduced susceptibility to UVA-induced DNA damage. 6-TG DNA in peripheral blood mononuclear cells remained measurable for over 2 years. Replacing azathioprine selectively reduced the skin photosensitivity to UVA, attenuated UVA-induced skin DNA damage, and is likely based on incorporated 6-TG in DNA.
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