title: Reversal of UVA skin photosensitivity and DNA damage in kidney transplant recipients by replacing azathioprine.
abstract: 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/cm(2)  (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.
authors.affiliation: Department of Dermatology, University Hospital Zürich, Switzerland. hofbauer@usz.ch
authors.forename: G F L
authors.initials: GF
authors.lastname: Hofbauer
authors.forename: N R
authors.initials: NR
authors.lastname: Attard
authors.forename: C A
authors.initials: CA
authors.lastname: Harwood
authors.forename: J M
authors.initials: JM
authors.lastname: McGregor
authors.forename: P
authors.initials: P
authors.lastname: Dziunycz
authors.forename: G
authors.initials: G
authors.lastname: Iotzova-Weiss
authors.forename: G
authors.initials: G
authors.lastname: Straub
authors.forename: R
authors.initials: R
authors.lastname: Meyer
authors.forename: Y
authors.initials: Y
authors.lastname: Kamenisch
authors.forename: M
authors.initials: M
authors.lastname: Berneburg
authors.forename: L E
authors.initials: LE
authors.lastname: French
authors.forename: R P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: P
authors.initials: P
authors.lastname: Karran
authors.forename: A L
authors.initials: AL
authors.lastname: Serra
mesh_terms: D001379:Azathioprine / Q000008:administration & dosage*; D004249:DNA Damage; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D012867:Skin / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D007166:Immunosuppressive Agents; D017319:Photosensitizing Agents; D001379:Azathioprine