Radiation-induced adaptive response for protection against micronucleus formation and neoplastic transformation in C3H 10T1/2 mouse embryo cells.
We have monitored the end points of cellular survival, micronucleus formation and neoplastic transformation frequency to assess adaptation to ionizing radiation in the C3H 10T1/2 mouse embryo cell system. Plateau-phase cells were pre-exposed to an adapting dose of 0.1 to 1.5 Gy low-dose-rate gamma radiation 3.5 h prior to an acute challenge dose of 4 Gy. No adapting dose improved clonogenic survival detectably, whether the cells were plated immediately after the acute exposure or held in plateau phase for 3.5 h before plating. However, all chronic adapting doses resulted in both a reduction in micronucleus frequency in binucleate cells and about a twofold reduction in neoplastic transformation frequency per viable cell when cells were subsequently exposed to the 4-Gy challenge dose. Our data suggest that a low-dose-rate pre-exposure to ionizing radiation induces an adaptive response in C3H 10T1/2 cells, and that this response enhances DNA double-strand break repair when cells are subsequently exposed to a second radiation dose. This enhanced repair appears to be error-free since these adapted cells are also less susceptible to radiation-induced neoplastic transformation.
Azzam
E I
EI
Radiation Biology Branch, Chalk River Laboratories, Ontario, Canada.
Raaphorst
G P
GP
Mitchel
R E
RE
D000222:Adaptation, Physiological / Q000528:radiation effects*; D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005720:Gamma Rays; D051379:Mice; D008809:Mice, Inbred C3H; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects*; D011836:Radiation Tolerance