Reduction of radiation-induced DNA damage by reciprocal paracrine interactions between normal human epithelial and mesenchymal cells

Abstract

Purpose Radiation response is complex especially when the effect is assessed in a tissue which naturally accommodates different types of cells. In this work we examined whether interactions between epithelial and mesenchymal cells can modulate the extent of radiation-induced DNA damage in one or both type of cells. Materials and Methods Human primary thyrocytes (PT, normal epithelial cells) and normal diploid fibroblasts (BJ, mesenchymal cells) after homologous or heterologous conditioned medium transfer were irradiated with a single acute dose of γ-rays. Radiation-induced DNA damage was evaluated in terms of the number γ-H2AX nuclear foci per cell or by Comet assay. Results Reciprocal conditioned medium transfer prior to irradiation resulted in the reduction of DNA damage in both types of cells indicating the involvement of paracrine soluble factors. The DNA-protected state of cells was achieved within minutes after heterologous conditioned medium transfer. The diminished DNA damage was not detected after reciprocal conditioned medium transfer between BJ and epithelial cancer cell lines. Conclusions The results imply the existence of paracrine soluble factor-mediated reciprocal interactions between normal epithelial and mesenchymal cells which protect DNA from radiation-associated genotoxic stress.