Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK.
Photochem Photobiol Sci. 2012 Jan;11(1):62-8. doi: 10.1039/c1pp05194f. Epub 2011 Aug 23.
The thiopurines azathioprine, 6-mercaptopurine and 6-thioguanine (6-TG) are important medications for cancer and inflammatory disorders. They are also widely prescribed as immunosuppressants in organ transplant patients. Their metabolism results in the incorporation of 6-TG into patients' DNA, and this increases skin sensitivity to incident UVA. Unlike the canonical DNA bases, which do not absorb UVA to a significant degree, DNA 6-TG is a strong UVA chromophore. It acts as a Type II UVA photosensitizer, and the combination of 6-TG and UVA treatment induces a synergistic toxicity in cultured human cells. Here, we review some of the damage that this interaction causes. Photochemical activation of DNA 6-TG triggers DNA and protein oxidation; it induces DNA breakage, DNA crosslinking, oxidation of DNA bases and the covalent attachment of proteins to DNA. Many of these photochemical DNA lesions are difficult for cells to deal with, and we review the evidence linking thiopurine immunosuppression with genome instability and the high incidence of skin cancer in organ transplant recipients.
硫嘌呤类药物巯嘌呤、6-巯基嘌呤和 6-硫鸟嘌呤（6-TG）是治疗癌症和炎症性疾病的重要药物。它们也被广泛用作器官移植患者的免疫抑制剂。这些药物的代谢会导致 6-TG 掺入患者的 DNA 中，从而增加皮肤对 UVA 照射的敏感性。与不显著吸收 UVA 的典型 DNA 碱基不同，DNA 6-TG 是一种强 UVA 发色团。它作为一种 II 型 UVA 光增敏剂，6-TG 和 UVA 联合治疗会在培养的人类细胞中诱导协同毒性。在这里，我们回顾了这种相互作用引起的一些损伤。DNA 6-TG 的光化学激活会触发 DNA 和蛋白质氧化；它会诱导 DNA 断裂、DNA 交联、DNA 碱基氧化以及蛋白质与 DNA 的共价结合。这些光化学 DNA 损伤中有许多是细胞难以处理的，我们回顾了证据，将硫嘌呤类免疫抑制与基因组不稳定性和器官移植受者中皮肤癌的高发联系起来。
