Analysis of gene expression profiles after irradiation of human cell lines

Abstract

To understand the genetic mechanisms associated with heterogeneity in radioresistance among human tumor cells, gene expression profiles of a set of tumor cell lines previously characterized for radiosensitivity were examined. Because there may be combinations of genes that are activated on irradiation after the cell acquires resistance to radiation, DNA microarray technology was used to study the total effects of multiple radioresistance genes.
Focusing on D₁₀, a total of 65 genes were identified that may be involved in cellular reproduction after irradiation. Relatively radioresistant cell lines (D₁₀ > 5Gy) were clearly distinguished from nonresistant cell lines (D₁₀ < 4Gy) at both 1 and 3 h after irradiation. Furthermore, using genes selected for altered transcription levels at both the 1 and 3 h time points after irradiation, the correct classification of another four radioresistant cell lines (5.95 < D₁₀ < 7.21 Gy) was confirmed.
Genes related to the inhibition of cell death and the promotion of proliferation were preferentially activated in radioresistant cell lines, whereas those associated with pro-apoptotic or cell communication functions were generally transcribed at a higher level in radiosensitive cell lines.