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X-ray repair cross-complementing 1 (XRCC1) is required for single-strand break repair in human cells and several polymorphisms in this gene have been implicated in cancer risk and clinical prognostic factors. We examined the frequency of the 5'-untranslated region (5'-UTR) variant -77T-->C (rs 3213235) in 247 French breast cancer (BC) patients, 66 of whom(More)
The X-ray repair cross complementing 1 (XRCC1) protein is required for viability and efficient repair of DNA single-strand breaks (SSBs) in rodents. XRCC1-deficient mouse or hamster cells are hypersensitive to DNA damaging agents generating SSBs and display genetic instability after such DNA damage. The presence of certain polymorphisms in the human XRCC1(More)
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(More)
Patients taking the immunosuppressant and anticancer thiopurines 6-mercaptopurine, azathioprine or 6-thioguanine (6-TG), develop skin cancer at a very high frequency. Their DNA contains 6-TG which absorbs ultraviolet A (UVA) radiation, and their skin is UVA hypersensitive, consistent with the formation of DNA photodamage. Here we demonstrate that UVA(More)
Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and(More)
Long-term treatment with the anticancer and immunosuppressant thiopurines, azathioprine or 6-mercaptopurine, is associated with acute skin sensitivity to ultraviolet A (UVA) radiation and a high risk of skin cancer. 6-thioguanine (6-TG) that accumulates in the DNA of thiopurine-treated patients interacts with UVA to generate reactive oxygen species. These(More)
The frequency of squamous cell skin carcinoma in organ transplant patients is around 100-fold higher than normal. This dramatic example of therapy-related cancer reflects exposure to sunlight and to immunosuppressive drugs. Here, we show that the interaction between low doses of UVA, the major ultraviolet component of incident sunlight, and 6-TG, a UVA(More)
Cutaneous photosensitization is a common side effect of drug treatment and can be associated with an increased skin cancer risk. The immunosuppressant azathioprine, the fluoroquinolone antibiotics and vemurafenib-a BRAF inhibitor used to treat metastatic melanoma-are all recognized clinical photosensitizers. We have compared the effects of UVA radiation on(More)
UNLABELLED The relationship between sun exposure and nonmelanoma skin cancer risk is well established. Solar UV (wavelength 280-400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280-320 nm). How the 20-fold more abundant UVA (320-400(More)
The thiopurines azathioprine and 6-mercaptopurine have been extensively prescribed as immunosuppressant and anticancer agents for several decades. A third member of the thiopurine family, 6-thioguanine (6-TG), has been used less widely. Although known to be partly dependent on DNA mismatch repair (MMR), the cytotoxicity of 6-TG remains incompletely(More)