Multiple forms of DNA damage caused by UVA photoactivation of DNA 6-thioguanine
Authors listReto Brem Peter Karran
Thiopurines are prescribed frequently as medication for cancer and for inflammatory disorders. One of them, azathioprine, has been the immunosuppressant of choice for organ transplant recipients for many years. Thiopurine use is associated with elevated sun sensitivity and skin cancer risk. Skin sensitization is selective for UVA. 6-TG integrates into DNA and unlike the canonical DNA bases, it is a strong UVA chromophore with an absorbance maximum at 342 nm. DNA 6-TG is a photosensitizer and a source of reactive oxygen species. Reactive oxygen that is generated from the photochemical activation of DNA 6-TG causes extensive damage to DNA and proteins. This damage is mutagenic and extremely toxic to cultured human cells. Here we describe some of the lesions that are known to be generated from UVA irradiation of DNA 6-TG. We discuss how this photochemical damage might contribute to the toxic effect of thiopurine/UVA treatment on cultured cells and to the high risk of skin cancer in thiopurine-treated patients.