Intercellular communication is involved in the bystander regulation of gene expression in human cells exposed to very low fluences of alpha particles.
We demonstrate by western analysis that the expression levels of TP53 (formerly known as p53), CDKN1A (formerly known as p21Waf1), CDC2 (formerly known as p34cdc2), CCNB1 (cyclin B1) and RAD51 are significantly modulated in confluent, density-inhibited human diploid cell populations exposed to doses where only a small fraction of the nuclei are actually traversed by an alpha-particle track. The extent of modulation of TP53 and CDKN1A is significantly reduced in the presence of the gap junction inhibitor lindane and in irradiated low-density cell populations. In situ immunofluorescence studies show that at doses where about 2% of the nuclei would be traversed by an alpha particle, induction of CDKN1A occurs in more cells than predicted. Furthermore, the induced cells are present in isolated aggregates of neighboring cells. Therefore, our studies at the gene expression level indicate that similar signaling pathways are induced in bystander cells that are not traversed by an alpha particle as in traversed cells, and that biological effects in cell populations are not restricted to the response of individual cells to the DNA damage they receive.
Azzam
E I
EI
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
de Toledo
S M
SM
Gooding
T
T
Little
J B
JB
D000512:Alpha Particles; D002450:Cell Communication / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000528:radiation effects; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53