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Transforming growth factor‐β1 enhances the lethal effects of DNA‐damaging agents in a human lung‐cancer cell line
Author(s) -
Raynal Stéphane,
Nocentini Silvano,
Croisy Alain,
Lawrence David A.,
Jullien Pierre
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970717)72:2<356::aid-ijc26>3.0.co;2-c
Subject(s) - mink , cisplatin , pyrimidine dimer , biology , cancer research , cell culture , dna damage , comet assay , cytokine , a549 cell , apoptosis , microbiology and biotechnology , transforming growth factor , cell growth , cancer cell , immunology , cancer , dna , genetics , chemotherapy , ecology
In tissue culture conditions, exogeneous active transforming growth factor‐β1 (TGF‐β1) 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the cytokine used alone is to inhibit reversibly the multiplication of the same cells without further impairing, once withdrawn from their environment, their capacity to divide and give rise to colonies.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‐β1 and UV‐C was studied on mink and human cell lines, and the biomodulation by TGF‐β1 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‐β1 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‐β1 might affect the curative and/or undesirable secondary side effects of cancer therapy. Int. J. Cancer 72:356–361, 1997. © 1997 Wiley‐Liss, Inc.