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-3H]thymidine, under the dorsal skin for 14 days. The animals were then placed on either a choline-supplemented 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 (t1/2) of liver cells, and the fractional rates of liver cell death (Kd) and proliferation (Kp). In rats fed the control choline-supplemented diet, liver cells were estimated to die at an overall Kd of 0.16% per day, and to have a t1/2 of 439.5 days; Kp was higher in younger than in older rats. In rats fed the choline-devoid diet, liver cells diet at a Kd ranging from 4.82 down to 0.93% per day, as the length of the feeding period increased; corresponding t1/2S were 14.3 and 74.6 days. In these rats, Kp 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.