SERINE HYDROXYMETHYLTRANSFERASE (SHMT) AS A PRECIOUS INDICATOR OF ANTIPROLIFERATIVE OR IMMUNOSUPPRESSIVE POTENCY OF VARIOUS COMPOUNDS

Measurements of Serine Hydroxymethyltransferase (SHMT) in resting lymp hocte cultures showed that the activity level of this enzyme is very l ow. Under the influence of mitogenic stimuli SHMT activity is induced 5-20 fold. Addition in the cultures of antiproliferative (AP) or immun osuppressive (IMS) agents, namely D-actinomycin, cytarabine, L-asparag inase and cyclosporin led to the following observations: 1. All AP and IMS agents, added to the lymphocyte culture 48 hrs after stimulation, cause a decrease in the mitogen induced activity of SHMT. The higher the concentration of the AP or IMS compound, the greater the decrease of the enzyme activity. 2. The observed activity changes are not, as o ne would expect, the same in the case of all four drugs. Higher inhibi tion of SHMT activity is produced by actinomycin (about 50%) and lower by cyclosporin (about 30%). Probably, each compound causes a differen t degree of inhibition, reflecting its specific mechanism of action. D ose titration experiments established the limit between active and ina ctive concentrations of the tested agents. The development of a simple test, based on SHMT activity estimation, for rapidly assessing a comp ound's antiproliferative or immunosuppressive potency is proposed. Als o, this test could be valuable for-the titration of substances tested and provide preliminary data concerning the doses that would be admini stered during clinical trials.