EFFECTS OF CREATINE AND BETA-GUANIDINOPROPIONIC ACID ON THE GROWTH OF EHRLICH ASCITES TUMOR-CELLS - IP INJECTION AND CULTURE STUDY

Growth of Ehrlich ascites tumor (EAT) cells in the abdominal space of mice or in cell culture was studied in response to i.p. injection or addition, respectively, of creatine or creatine analogue beta-guanidinopropionic acid (beta-GPA). The increase in body weight of the mice due to cancer growth was less in the beta-GPA-injected than in the creatine- or sham-injected group. The volume of abdominal ascites and total cell counts at 11th day after implantation of EAT cells was significantly less in the beta-GPA than in the other groups. The proliferation rate of EAT cells in the beta-GPA group was 27% and 35% of the creatine- and sham-injected groups, respectively. Supplementation of creatine tended to enhance the growth of EAT cells. The creatine concentration in ascites fluid was approximately 4-times greater than in blood plasma of sham-injected control mice. But the creatine content in EAT cells was significantly reduced to approximately 50% in response to beta-GPA injection. Cell culture without creatine caused a significant decrease in viability. The viability was improved, however, by addition of either creatine or serum into the medium. By contrast, it was not significantly increased by addition of serum alone which caused only a minor elevation of the creatine level (23 mu M). It is suggested that EAT cell growth is inhibited by lowering the availability of creatine in association with some unknown factors in serum or ascites fluid.