Liver cell turnover in rats fed a choline-devoid diet

Abstract

Liver DNA was labeled in a group of weanling Fischer-344 male rats by placing mini-osmotic pumps, loaded with [methyl- ³ H]thymidine, under the dorsal skin for 14 days. The animals were then placed on either a cholinesupplemented or a choline-devoid diet, and subgroups on each diet were killed after 1, 2, 4, 8 and 16 weeks. Liver DNA total and specific radioactivities were determined in all rats. The results were used to estimate the half-life ( t ½) of liver cells, and the fractional rates of liver cell death ( K_d and proliferation ( K_p ). In rats fed the control choline-supplemented diet, liver cells were estimated to die at an overall K d of 0.16% per day, and to have a t, h of 439.5 days; K_p was higher in younger than in older rats. In rats fed the choline-devoid diet, liver cells died at a K_d ranging from 4.82 down to 0.93% per day, as the length of the feeding period increased; corresponding t ½ were 14.3 and 74.6 days. In these rats, K_p was more than sufficient to compensate for cell loss. The results show that liver-cell death represents a major consequence of feeding a choline-devoid diet to rats, and that the necrogenic action of the diet is a major factor responsible for the highly increased turnover of liver cells present in these animals. However, evidence was obtained that the diet has also a primary mitogenic action, beyond those related to replacement of dead cells, and to cell accretion due to normal growth of the animals and the liver.