Evidence for a special relationship between proteolysis and single cell necrosis

Abstract

A high rate of single cell necrosis is a common phenomenon in neoplastic and preneoplastic lesions, accounting for growth rates that are significantly less than the cell birth rate. We present data relating the process of protein turnover to single cell necrosis. Cells were labeled with 3H-leucine and 14C-thymidine; the loss of radioactivity from the cell protein and DNA was then measured for 3-6 days. Preliminary experiments showed that cell necrosis by freeze-thawing cells did not significantly contribute to the degradation of cell proteins. Similar results were observed with dying 3T3-SV40 cells at high density. L-cells, however, showed a progressive increase in cell loss as higher cell densities were attained on the monolayer. Although proteolysis remained constant in the culture, analysis of the cells recovered from the high density monolayers showed little loss of labeled protein after adjustment for loss of label in the DNA. Three possible explanations are proposed: DNA turns over with cell protein (unlikely), single cell necrosis involves a special mechanism that facilitates reutilization of amino acids, or single cell necrosis includes only cells that are selectively involved in protein turnover. A unique relationship between single cell necrosis and proteolysis is suggested.