Effect of the cancer recognition, immunedefense suppression, and serine protease protection peptide on DNA synthesis in rat hepatocytes and human lymphocytes.

The cancer recognition, immunedefense suppression, and protease protection (CRISPP) peptide produced by cancer cells enhanced DNA synthesis in primary cultures of rat hepatocytes and in human peripheral blood lymphocytes. In 72-h hepatocyte cultures, increasing doses of the CRISPP peptide increased DNA synthesis, as judged by 3H-thymidine incorporation, from 35.2% above the peak incorporation value observed when the hepatocytes are induced to undergo DNA synthesis by 10 ng/ml of EGF when 0.01 ng/ml of the CRISPPS peptide is used to 130.5% at 100 ng/ml of the peptide. The CRISPPS peptide also enhanced DNA synthesis in PHA stimulated human peripheral blood lymphocytes (HPBL) in 72-h cultures. A bell-shaped concentration dependence was observed in HPBL, with a maximum increase in 3H-thymidine uptake of 248% at 1 ng/ml of the CRISPPS peptide. The effect decreased to 26% at 100 ng/ml. The difference in the concentration dependence between hepatocytes and HPBL could be due to specific cell types and culture conditions, and/or to differences in the biochemical pathways leading to DNA synthesis as induced by EGF and PHA. Since the CRISPP peptide protects serine proteases against inhibition by the alpha 1-protease inhibitor, different biochemical pathways might require participation and/or timing of limited proteolytic controls to a different extent. In both cases, the protective effect of the CRISPP peptide could amplify and/or prolong the activities of the intracellular proteases involved in the mitogenic processes.