Repair of Potentially Lethal Damage in Rat Mammary Clonogens Following Irradiation in Organoid Culture

Abstract

In the course of investigations of radiogenic neoplasia in mammary cells in vivo, post-irradiation repair of potentially lethal damage (PLDR) was previously observed in mammary epithelial clonogens when they were irradiated and left in their tissue environment for 4-24 h after exposure. This type of PLDR increases the initial shoulder of the survival curve without significantly affecting its terminal slope. It has since been described in similarly treated thyroid and hepatic clonogens, and significantly exceeds that generally seen in most mammalian cells in culture. In this study, a ten-fold increase in the concentration of mammary clonogens which could be assayed was achieved by the isolation and short term culture (2-4 days) of mammary organoids (ductal and end-bud fragments). Assays of clonogen concentrations were carried out with cell suspensions prepared immediately following irradiation of 4-day organoid cultures or 24 h after irradiation of such organoid cultures. A near four-fold increase in clonogen survival was observed with the delay in assay after irradiation; this is comparable to the PLDR seen in mammary clonogens irradiated and left in situ for 4-24 h after exposure.