Department of Nephrology and Hypertension, Rabin Medical Center, Petah-Tikva, Israel.
Biomed Pharmacother. 2012 Sep;66(6):409-13. doi: 10.1016/j.biopha.2012.06.001. Epub 2012 Jun 30.
Immunosuppressive treatment increases the risk of post-transplant cancer. Cyclosporine reduced UV-induced DNA repair by peripheral blood mononuclear cells (PBMC) and increased cancer incidence in kidney transplant recipients. Calcineurin inhibitors (CNI), but not mammalian target of rapamycin (mTOR) inhibitors or mycophenolic acid, suppressed H₂O₂-induced DNA repair in human peripheral blood mononuclear cells (PBMC) in vitro at maintenance drug concentrations. DNA repair, when measured in quiescent cells, is named spontaneous DNA repair, and represents a basal ongoing DNA repair in response to endogenous DNA damage. The effect of immunosuppressive drugs on spontaneous DNA repair has not been investigated.
To investigate the effect of currently used immunosuppressive drugs on spontaneous DNA repair.
Spontaneous DNA repair by human PBMC was tested in vitro in the presence of the CNI-cyclosporine and tacrolimus; mycophenolic acid (MPA); and the mTOR inhibitors-sirolimus and everolimus, at low to high nontoxic concentrations.
Cyclosporine and tacrolimus suppressed spontaneous DNA repair throughout the tested dose range. In contrast, MPA, sirolimus and everolimus did so only at the high doses.
A reduction in CNI dosage may lead to a decrease in the occurrence of post-transplant malignancy.
免疫抑制治疗会增加移植后癌症的风险。环孢素会降低外周血单核细胞（PBMC）的紫外线诱导 DNA 修复能力，并增加肾移植受者的癌症发病率。钙调神经磷酸酶抑制剂（CNI），而不是哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂或霉酚酸，会在维持药物浓度下抑制体外人外周血单核细胞（PBMC）中 H₂O₂诱导的 DNA 修复。在静止细胞中测量的 DNA 修复被命名为自发 DNA 修复，代表了对内源性 DNA 损伤的基本持续 DNA 修复。免疫抑制药物对自发 DNA 修复的影响尚未得到研究。
研究目前使用的免疫抑制药物对自发 DNA 修复的影响。
在存在 CNI-环孢素和他克莫司、霉酚酸（MPA）和 mTOR 抑制剂-西罗莫司和依维莫司的情况下，在低到高无毒浓度下，体外测试人 PBMC 的自发 DNA 修复。
环孢素和他克莫司在整个测试剂量范围内抑制自发 DNA 修复。相比之下，MPA、西罗莫司和依维莫司仅在高剂量时才会这样做。
减少 CNI 剂量可能会降低移植后恶性肿瘤的发生。
