Streaming liver. VII: DNA turnover in acinus zone-3.

Livers of four young, male, random-bred rats weighing 250 g were fixed in formalin and stained with Feulgen. In each section, 50 hepatocytes were randomly selected and their distance from the nearest terminal hepatic vein was measured with an eye-piece micrometer. Distance was expressed in two units: 1. micrometer and, 2. cell location, or the cell number separating a sampled cell from the terminal hepatic rim. The sections were scanned with an image cytometer. The tissue was magnified x 400 and digitized into 512 x 512 pixels. The software determined the nuclear boundary and estimated its area and optical absorbance, which was expressed in relative DNA units. One unit equals the absorbance of a diploid lymphocyte. Nuclear area and optical absorbance measurements were made up to 220 microns distance from the terminal hepatic vein which roughly covers zones 2 and 3. Previously we have shown that in zones 1 and 2 hepatocyte nucleus enlarges and becomes polyploid. The present study demonstrates that in zone-3 this trend is reversed, nuclear area and DNA absorbance decline. The average hepatocyte advances 2 microns daily. In zone-1 it accumulates daily 0.005 DNA absorbance units and in zone-3 it loses daily 0.24 DNA absorbance units. It is proposed that in zone-3 DNA leaves the intact cell in a physiological way. DNA accumulation and polyploid are regarded here as forms of gene amplification which may be reversed, so that under these circumstances amplified DNA may be "deamplified" and the excess DNA leaves the cell.