Low doses of alpha particle irradiation modify the expression of genes regulating apoptosis in human MCF-7 breast cancer cells.
The possibility of modifying apoptosis-related genes in tumor cells is an interesting line of research that calls for multidisciplinary experimentation to describe its characteristics and the conditions required. In vitro low doses of alpha particle irradiation due to radon have an antiproliferative effect on the growth of MCF-7 cells and increase the sensibility of cancer cells to taxol, a chemotherapeutic agent that induces cellular apoptosis. The present study examines the in vitro effects of low doses of alpha particle irradiation from the gas radon on the expression of some bcl-2 family apoptosis-related genes. The analyzed genes were bax, bcl-2 and bcl-x, with known responses to genotoxic stress (bcl-2) or ionising radiation (bax and bcl-x) in MCF-7 human breast cancer cells. The results obtained indicate that the cell line studied expresses the mentioned genes and they demonstrate that irradiation with low radon doses of MCF-7 cells induces underexpression of both bax and bcl-2 genes. Interestingly, the mRNA levels of the full-length bcl-x gene (bcl-xL) were overexpressed after irradiation, and we found significant mRNA levels of an alternative mRNA splicing form of the same gene (bcl-xS), which enhances the apoptotic sensitivity of the cell. The increased sensitivity to apoptosis resulting from bcl-xS overexpression is important because it might improve the efficacy of chemotherapeutic agents used to treat cancers which act through induction of apoptosis. The finding that low radiation doses of alpha particles from the gas radon modulate the expression of apoptosis-related genes suggests a therapeutic utility for this naturally occurring agent.
Soto
Jesús
J
Department of Medical Physics, School of Medicine, University of Cantabria, 39011 Santander, Spain.
Sainz
Carlos
C
González-Lamuño
Domingo
D
Cos
Samuel
S
D000512:Alpha Particles; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D008969:Molecular Sequence Data; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051028:bcl-2-Associated X Protein / Q000235:genetics; D051020:bcl-X Protein / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein