Transforming growth factor-beta 1 enhances the lethal effects of DNA-damaging agents in a human lung-cancer cell line

In tissue culture conditions, exogeneous active transforming growth factor-beta 1 (TGF-beta 1) 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 sore 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the cytokine used alone is to inhibit reversibly the multiplication of the same cells without further impairing, once withdrawn from their environment, their capacity to divide and give rise to colonies, The lethal synergy between TGF-beta 1 and UV-C was studied on mink and human cell lines, and the biomodulation by TGF-beta 1 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-beta 1 appears to enhance apoptosis rather than to disturb the repair of DNA photole-sions (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-beta 1 might affect the curative and/or undesirable secondary side effects of cancer therapy. (C) 1997 Wiley-Liss, Inc.