PARENT SESSION
9:00 AM to 11:00 AM
Wednesday, April 24, 2002
Symposium 19
Michael Fry Award Symposium
Room: Tahoe
(S19-2) Mechanisms Underlying the Transmission of Stress from Irradiated to non-Irradiated Cells.
Azzam, Edouard*,1,2, de Toledo, Sonia1,2, Little, John2, 1 New Jersey Medical School, Newark, NJ2 Harvard School of Public Health, Boston, MA
ABSTRACT-
Increasing experimental evidence indicates that traversal through the nucleus of a cell by an ionizing particle or photon is not a pre-requisite to elicit a radiation response. Non-traversed bystander cells that are in the vicinity of irradiated cells or recipients of growth medium from radiation-exposed cultures have been shown to exhibit responses similar to those of irradiated cells. Changes in gene expression, induction of genetic changes including DNA damage, lethality and transformation to the neoplastic state have been observed in bystander cells of various types suggesting that these cells contribute to the risk of exposure to ionizing radiation. An understanding of the basic mechanisms by which damage effects are transmitted from irradiated to non-irradiated cells is emerging. We have previously provided direct evidence for the participation of connexin43-mediated gap-junction intercellular communication in bystander effects observed in confluent cultures of human and rodent cells exposed to low-fluences of 
-particles. We now show that irradiated cells can communicate via gap-junctions with neighboring non-irradiated cells, and present preliminary evidence for the modulation of connexin43 mRNA levels in low-fluence -particle irradiated normal human cells. Furthermore, data that support the involvement of oxidative metabolism in the bystander response will be also presented. These latter data indicate that superoxide anions and hydrogen peroxide produced by metabolic processes are specific reactive oxygen species that affect the expression of biological changes in bystander cells after the initial radiation exposure.
KEYWORDS: bystander effect, gap-junctions, connexin43, reactive oxygen species