CONTROL OF RATE AND EXTENT OF THE PROLIFERATIVE RESPONSE AFTER PARTIAL-HEPATECTOMY

To examine the role of the early changes occurring in the liver within the first hours after a partial hepatectomy and in an attempt to demo nstrate the involvement of subsequent regulatory mechanisms, the size of the remnant liver was modified at various times and by different su rgical techniques. Male Wistar rats were submitted to a two-thirds ''t emporary partial hepatectomy'' produced by a 3-h occlusion of the pedi cle of the anterior lobes protected by local hypothermia. Various inde xes of cell proliferation ([H-3]thymidine uptake and 5-bromo-2'-deoxyu ridine and proliferating cell nuclear antigen labeling) were not incre ased despite a c-myc expression as high as that observed after a two-t hirds partial hepatectomy. The temporary partial hepatectomy and a sha m operation induced modifications of the hepatocytes, allowing rapid D NA synthesis after a subsequent two-thirds partial hepatectomy. After this initial nonspecific response, the extent of the regenerative resp onse is determined according to the size of the liver mass present app roximately from the 10th to the 18th hour after the initial stimulus. For instance, when st one-third partial hepatectomy was converted into a two-thirds partial hepatectomy at the 10th hour, the DNA synthesis at the 24th hour reached the value observed after a straightforward tw o-thirds partial hepatectomy. Inversely, the regenerative response was significantly reduced when additional liver lobes were connected to n eck Vessels between the 14th and the 18th hour after a two-thirds part ial hepatectomy. In conclusion, the actual liver mass present during t he period corresponding to mid-to late G(1) appears to control the mag nitude of the proliferative response, which is not the simple conseque nce of the early changes following a partial hepatectomy.