ALLYLAMINE ENHANCES C-HA-RAS PROTOONCOGENE EXPRESSION IN RAT AORTIC SMOOTH-MUSCLE CELLS

Studies were conducted to evaluate the mechanisms involved in the deregulation of proliferative control induced by allylamine (AAM) in rat aortic smooth muscle cells (SMCs). Subcultured SMCs from animals treated with AAM (70 mg/kg) or tap water for 20 days were processed for measurements of [H-3]thymidine incorporation and c-Ha-ras mRNA levels. Pre-confluent AAM cells stimulated with 10% fetal bovine serum exhibited enhanced mitogenic responsiveness relative to control cells. Decreased [H-3]thymidine incorporation was observed in post-confluent cultures of both cell types relative to pre-confluent counterparts. A 5-fold increase in c-Ha-ras transcript levels was observed in pre-confluent/cycling cultures of AAM cells relative to controls. C-Ha-ras expression was markedly reduced in post-confluent cultures of both cell types as compared to pre-confluent counterparts. No difference between control and AAM cells was observed during G1-synchronization of pre- or post-confluent cultures. These results suggest that the enhanced proliferative capacity induced by AAM is associated with alterations in cell cycle-related expression of the c-Ha-ras protooncogene.