Partial liver irradiation in rats induces the hypertrophy of nonirradiated liver lobes through hepatocyte proliferation†.

Abstract

Irradiation of the liver induces a regenerative response in the nonirradiated part of the liver. It is unclear whether this leads to actual liver enlargement. The aim of this study was to evaluate the weight of compensatory hypertrophy that occurs in nonirradiated livers and to clarify the mechanism of hypertrophy from the viewpoint of hepatocyte proliferation. The anterior liver lobes (anterior lobes) were irradiated with 60Gy of X-rays (X60Gy) under opening laparotomy. Body weights and liver lobe weights were measured before and at 1, 4, 8 and 12weeks after irradiation, and serum and liver tissue samples were analyzed at each time point. The anterior lobes atrophied progressively, whereas the posterior liver lobes (posterior lobes) hypertrophied in the X-ray irradiated (X-irradiated) group. Although temporary liver damage was observed after irradiation, liver function did not decrease at any time point. Hepatocyte degeneration and loss were observed in the anterior lobes of the X-irradiated group, and significant fibrosis developed 8weeks postirradiation. Following irradiation, the proportion of Ki-67-positive cells in the anterior lobes decreased markedly in the early postirradiation period, whereas the proportion of positive cells in the posterior lobes increased, peaking at 4weeks postirradiation (P < 0.05). Increased tumor necrosis factor-α expression was observed only in the anterior liver lobes of the X-irradiated group at 1 and 4weeks postirradiation. Partial liver irradiation with X60Gy induced compensatory hypertrophy of nonirradiated liver lobes. This study suggests that liver hypertrophy after partial liver irradiation is caused by increased hepatocyte mitosis.