Radioadaptive Response in Human Lymphocytes in Vitro

Abstract

Exposure to low doses of radiation and/or chemicals can prime an organism to withstand the stress of a subsequent exposure to higher doses of the same agent. In the case of radiation, this phenomenon has been called radioadaptive response. Cytogenetic studies have been undertaken in human lymphocytes to investigate adaptive response (AR) to ionizing radiation, in particular to seek the role of variables such as priming dose, cell cycle stage, and age and gender of the donor. We demonstrated that pre-exposure of lymphocytes in whole blood cultures to very low doses in the range of about 1 cGy (priming or adaptive dose [AD]) reduced the frequency of micronuclei in binucleated cells induced by 100 cGy--that is, produced an AR in these cells in vitro. However, pre-exposure of cells to 10.0 cGy did not reduce the chromosomal damage (micronuclei) induced by the challenging dose (CD) of 100 cGy under the same protocol, thus exhibiting an inverse dose-response relationship. There was marked variability in the AR among the individuals investigated in the study. The extent of AR also depended on the stage of cell cycle exposed to the CD of radiation. Maximum AR was observed when CD of 100 cGy was given 4 hours after AD, 30 hours following the mitogenic stimulation of lymphocytes. The least AR was observed when CD was given 48 hours after stimulation. Interestingly, AR was also found to be dependent on the age of the donor, a decrease in AR being observed with an increasing age. No significant difference in AR was observed between male and female donors. To understand the molecular events underlying AR, protein synthesis patterns were studied in human lymphocytes subjected to mitogen, heat, or radiation stress. Heat shock (45 degrees C, for 15 min) induced 7 proteins with molecular weights ranging from 40 to 80 kDa, while treatment with phytohemagglutinin (40 microg/mL) showed induction of 2 proteins of molecular weights 38 and 48 kDa, respectively. However, exposure of human lymphocyte cultures to gamma radiation did not significantly induce synthesis of any protein, up to 800 cGy dose. Lack of induction of proteins by gamma radiation in human lymphocytes contrasts with the previous reports showing X-ray radiation-enhanced gene expression in melanoma cells and/or human tumor fibroblasts.