Edouard I. Azzam

Transmission of damage signals from irradiated to nonirradiated cells

Abstract Confluent monolayer cultures of human and rodent cells were exposed to very low fluences of alpha particles, fluences whereby as few as 1% of the cell nuclei were traversed by an alpha track and received any radiation exposure. An elevated frequency of micronuclei, a surrogate measure of DNA damage, and of HPRT mutations were observed in the nonirradiated “bystander” cells. This was associated with an ATM-dependent upregulation of the p53 damage-response pathway. Damage signals were transmitted from irradiated to nonirradiated cells in the population by gap junction mediated intercellular communication. The biological effects in bystander cells appeared to be associated with oxidative stress, consistent with the observation that most of the mutants induced by very low fluences of alpha particles were a result of point mutations rather than deletions. Preliminary evidence suggests that activation of oxidative stress-responsive signal pathways may also occur in bystander cells. These findings, particularly the evidence for the induction of mutations in nonirradiated bystander cells after irradiation with very low fluences of alpha particles, could be of significance in estimations of the risk of residential radon exposure in human populations.