Early and late changes in radiation-induced gene expression arrays following radioprotection with amifostine

Abstract

Aims and Objectives: The study objective was to investigate differential gene expression in lymphohematopoietic tissues (spleens) of mice injected with amifostine and exposed to sublethal doses of 60Co γ-radiation. Materials and Methods: Differential cDNA gene expression arrays were used to examine early- (1 day) and late-occurring (63 days) changes in C3H/HeN mice that were administered either amifostine (100 mg/kg) or vehicle 30 min prior to exposure. Results: Sublethal irradiation initiated both early- and late-arising gene responses that were both specific and global in nature, with some significantly modified by amifostine. Of the early changes, ~15% of the genes were upregulated, whereas a comparable fraction was downregulated by irradiation. Notably, amifostine prophylaxis resulted in significant dampening of irradiation-related gene activity. Late-occurring changes were characterized by a reduction in fractional size (~11%) of upregulated genes, along with a corresponding increase of the downregulated fraction (~17%). Again, amifostine prophylaxis resulted in a significant dampening of gene activity, but only for downregulated genes. A cohort of pr oto-oncogenes responded comparably to the entire group of arrayed genes but with several notable exceptions. Differences in gene expression induced by sublethal whole-body radiation exposure were observed here within the splenic tissues of mice, and amifostine prophylaxis significantly altered patterns of gene expression within a sizable fraction of the arrayed genes. Conclusion: This study continues to illustrate the utility of differential cDNA array assays in identifying and dissecting critical gene events (e.g., hematopoietic growth factors and associated proto-oncogenes) altered by irradiation and by the radioprotective pharmacologic amifostine.