The survival of parenchymal hepatocytes irradiated with low and high LET radiation

We have developed an in vivo clonogenic assay system for parenchymal hepatocytes which has enabled us to investigate the reproductive survival and repair capacity of liver cells exposed to genotoxic agents. In this report we present our results with hepatocytes irradiated 60Co and neutrons. The survival curve for parenchymal hepatocytes enzymatically dispersed 30 min after exposure to 60Co has a D0 value of 2.7 Gy and an extrapolation number insignificantly different from unity. However, when the hepatocytes were allowed to remain in situ for 24 h before being assayed for survival, the extrapolation number significantly increased to 2.3, whereas the D0 value remained unchanged. Therefore, normal parenchymal hepatocytes in G0 are able to repair potentially lethal damage (PLD) after exposure to 60Co and this repair phenomenon is expressed solely as an increase in the n value. In contrast, with hepatocytes exposed to 14.3 MeV neutrons, the survival curve is exponential with a D0 value of 1.7 Gy regardless of whether the cells remained in situ for 30 min or 24 h before the assessment of their reproductive survival. A comparison of the 60Co and neutron survival curves, where 24 h is allowed for PLD repair to occur, demonstrates that the RBE of neutrons for hepatocytes increases with decreasing dose and equals 4.2 at 50 cGy. The radioprotective agent WR-2721 was shown to act as a dose modifying agent with a DMF of 2.1, implying that it may be of potential clinical value as a radiation hepato-protective drug.