Abstract
Papillary thyroid carcinoma (PTC) is a well-known type of radiation-induced malignancy in man. PTC tissue consists not only of epithelial but also of other types of cells, including those of mesothelial origin that form tumor stroma. To better understand the particularities of radiation-induced DNA damage in the thyroid, in this work we used model cultures composed of primary human thyrocytes (PT), normal diploid fibroblasts (BJ) and their mixtures to examine γH2AX foci after exposure.
In mixed cultures, the kinetics of γH2AX foci number changes was dose-dependent and similar to that in monocultures of BJ and PT. However, the numbers of γH2AX foci in mixed cultures was significantly lower in both types of cells comparing to monocultures. To investigate the mechanism of the protective effect, we studied the role of gap junction intercellular communications (GPIC). Blockage of GPIC with lindane lead to the increase in radiation-induced γH2AX foci numbers both in monocultures and mixed cultures in both BJ and PT, but the extent of γH2AX foci numbers restoration in mixed cultures did not reach the levels observed in monocultures, indicating that GJIC are only partly responsible for the diminished DNA damage.
Mixed cultures of BJ fibroblasts and PT display lower levels of radiation-induced DNA damage than in monoculture suggestive of the involvement of paracrine factors. Efficacy of DNA repair is not changed in mixed cultures. In the unfavorable environment leading to GJIC dysfunction, extent of DNA damage is higher then under normal conditions.
