Raynal S, Nocentini S, Croisy A, Lawrence D A, Jullien P
UPR42 du CNRS, Institut de Recherches sur le Cancer, Villejuif, France.
Int J Cancer. 1997 Jul 17;72(2):356-61. doi: 10.1002/(sici)1097-0215(19970717)72:2<356::aid-ijc26>3.0.co;2-c.
In tissue culture conditions, exogeneous active transforming growth factor-beta1 (TGF-beta1) enhances the lethal effect of DNA-damaging agents (UV-C, gamma rays, cisplatin, methotrexate and 5-fluorouracil) toward human A549 cells and mink Mv1Lu cells, as detected by the loss of their capacity to give rise to colonies; both these cell lines harbor a wild-type p53, as determined by immunoprecipitation. Contrastingly, the sole effect of the cytokine used alone is to inhibit reversibly the multiplication of the same cells without further impairing, once withdrawn from their environment, their capacity to divide and give rise to colonies. The lethal synergy between TGF-beta1 and UV-C was studied on mink and human cell lines, and the biomodulation by TGF-beta1 of cell killing by cisplatin, gamma rays, 5-fluorouracil or methotrexate was tested only on human cells. As investigated with UV-C-irradiated human A549 cells, TGF-beta1 appears to enhance apoptosis rather than to disturb the repair of DNA photolesions (mainly pyrimidine dimers) by the nucleotidic excision repair pathway according to results of nucleosomal ladder and comet tests. Our data raise the possibility that, in vivo, TGF-beta1 might affect the curative and/or undesirable secondary side effects of cancer therapy.
在组织培养条件下，外源性活性转化生长因子-β1（TGF-β1）增强了DNA损伤剂（紫外线C、γ射线、顺铂、甲氨蝶呤和5-氟尿嘧啶）对人A549细胞和貂Mv1Lu细胞的致死作用，这可通过它们形成集落能力的丧失来检测；通过免疫沉淀法确定，这两种细胞系都含有野生型p53。相反，单独使用这种细胞因子的唯一作用是可逆地抑制相同细胞的增殖，一旦将其从环境中移除，并不会进一步损害它们分裂和形成集落的能力。在貂和人细胞系上研究了TGF-β1与紫外线C之间的致死协同作用，并且仅在人细胞上测试了TGF-β1对顺铂、γ射线、5-氟尿嘧啶或甲氨蝶呤引起的细胞杀伤的生物调节作用。根据核小体梯度和彗星试验的结果，在用紫外线C照射的人A549细胞中进行研究时，TGF-β1似乎增强了细胞凋亡，而不是干扰核苷酸切除修复途径对DNA光损伤（主要是嘧啶二聚体）的修复。我们的数据提出了一种可能性，即在体内，TGF-β1可能会影响癌症治疗的疗效和/或不良的继发性副作用。
