Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
Add more filters










Database
Language
Publication year range
6.
Am J Transplant ; 12(1): 218-25, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21943390

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.


Subject(s)
Azathioprine/administration & dosage , DNA Damage , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Photosensitizing Agents/administration & dosage , Skin/radiation effects , Ultraviolet Rays , Humans
7.
Br J Cancer ; 99(8): 1276-84, 2008 Oct 21.
Article in English | MEDLINE | ID: mdl-18854826

ABSTRACT

The immunosuppressant azathioprine is used to prevent graft rejection after organ transplantation. To investigate whether azathioprine-associated mutagenesis contributes to the high incidence of skin tumours in organ transplant recipients (OTRs), we analysed PTCH gene mutations in 60 basal cell carcinomas (BCC); 39 from OTRs receiving azathioprine and 21 from individuals never exposed to azathioprine. PTCH was mutated in 55% of all tumours, independent of azathioprine treatment. In both the azathioprine and non-azathioprine groups, transitions at dipyrimidine sequences, considered to indicate mutation by ultraviolet-B radiation, occurred frequently in tumours from chronically sun-exposed skin. In BCC from non-sun-exposed skin of azathioprine-treated patients, there was an over-representation of unusual G:C to A:T transitions at non-dipyrimidine sites. These were exclusive to the azathioprine-exposed group and all in the same TGTC sequence context at different positions within PTCH. Meta-analysis of 247 BCCs from published studies indicated that these mutations are rare in sporadic BCC and had never previously been reported in this specific sequence context. This study of post-transplant BCC provides the first indication that azathioprine exposure may be associated with PTCH mutations, particularly in tumours from non-sun-exposed skin.


Subject(s)
Azathioprine/adverse effects , Carcinoma, Basal Cell/genetics , Immunocompromised Host/genetics , Immunosuppressive Agents/adverse effects , Receptors, Cell Surface/genetics , Skin Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Basal Cell/chemically induced , Carcinoma, Basal Cell/immunology , Female , Graft Rejection/prevention & control , Humans , Male , Middle Aged , Mutation , Organ Transplantation/adverse effects , Patched Receptors , Patched-1 Receptor , Polymerase Chain Reaction , Skin Neoplasms/chemically induced , Skin Neoplasms/immunology , Sunlight/adverse effects
SELECTION OF CITATIONS
SEARCH DETAIL
...