Radiation hepatology of the rat: time-dependent recovery

Abstract

In situ recovery kinetics of gamma-irradiated rat livers was investigated. To measure short-term repair, surgically exposed livers were irradiated with a 12.5-Gy priming dose. At various times (0-24 h) the liver was re-exposed surgically to 10 Gy. To measure long-term recovery, rats were exposed to a 10-Gy priming dose to the upper abdomen to irradiate the whole liver. The liver was then re-exposed surgically and given graded test doses 0 to 56 days after the first exposure. Repair as a function of interfraction interval (1-12 h) between eight fractions of 3 Gy to the upper abdomen followed 2 weeks later by an 10-Gy top-up dose to the exposed liver was also investigated. Approximately 3 months after the last exposure plasma aspartate aminotransferase, retention of intravenously injected rose bengal, liver weight, and hydroxyproline content were measured to determine hepatic necrosis, function, mass, and fibrosis, respectively. A 15-Gy single-exposure threshold dose was needed to produce detectable hepatic injury. Exceeding this threshold dose resulted in a dose-dependent increase in liver injury as measured by all four end points. Split-dose irradiation with a 10-Gy priming dose and an interfraction interval of 1 day increased the isoeffect dose by 3.9 to 5.8 Gy. Increasing the interfraction interval from 1 to 56 days did not further increase the isoeffect dose. Exposing the liver to eight fractions of 3 Gy with an interfraction interval of 3 h or longer resulted in a dose recovery of approximately 80% (i.e., 19 Gy). A substantial portion of this recovery was evident with interfraction intervals of 1 h. A fluctuating repair pattern with increasing time (0 to 24 h) between 12.5 and 10.0 Gy liver irradiation was observed. This repair was characterized by a 1-h delay after irradiation, followed by near complete repair during the next 3 h, followed by sensitization during the next 2 h and a second wave of repair between 8 and 24 h. Repair was not completed until 21 h after irradiation. It is concluded that the liver's capacity to repair injury within 24 h is similar to that of other late-responding tissues. However, there is no additional repair after 24 h, indicating an absence of slow repair.