Genotoxic damage in non-irradiated cells: contribution from the bystander effect.
It has always been accepted dogma that the deleterious effects of ionising radiation such as mutagenesis and carcinogenesis are due mainly to direct damage to DNA. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, it is shown here that non-irradiated cells acquire the mutagenic phenotype through direct contact with cells whose nuclei are traversed with 2 alpha particles each. Pre-treatment of cells with lindane, a gap junction inhibitor, significantly decreased the mutant yield. Furthermore, when irradiated cells were mixed with control cells in a similar ratio as the in situ studies, no enhancement in bystander mutagenesis was detected. Our studies provide clear evidence that genotoxic damage can be induced in non-irradiated cells, and that gap junction mediated cell-cell communication plays a critical role in the bystander phenomenon.
Zhou
H
H
Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Randers-Pehrson
G
G
Suzuki
M
M
Waldren
C A
CA
Hei
T K
TK
D000512:Alpha Particles; D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects; D018957:CD59 Antigens / Q000235:genetics / Q000528:radiation effects; D016466:CHO Cells; D002470:Cell Survival / Q000528:radiation effects; D006224:Cricetinae; D004249:DNA Damage / Q000528:radiation effects; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology* / Q000528:radiation effects; D016296:Mutagenesis; D016133:Polymerase Chain Reaction
D018957:CD59 Antigens
Non-programmatic