Effect of combination of deoxypyridoxine with known anti-proliferative or immunosuppressive agents on lymphocyte serine hydroxymethyltransferase

Measurements of serine hydroxymethyltransferase (SHMT) in resting lymphocyte cultures showed that the level of activity of this enzyme is very low. Under the influence of mitogenic stimuli serine hydroxymethyltransferase activity is induced 5-20-fold. Addition in the cultures of 4-deoxypyridoxine (dB6), a potent antagonist of vitamin B6 coenzymes, concurrently with the mitogen, inhibits the induction of SHMT. Separate addition in the cultures of four anti-proliferative (AP) and immunosuppressive (IMS) agents, namely actinomycin, cytarabine, asparaginase and cyclosporine, led to the following observations. (1) The AP and IMS agents produce a decrease in the mitogen-induced activity of SHMT. The higher the concentration of the AP/IMS compound, the greater the decrease of enzymatic activity. (2) When a AP/IMS agent is combined with dB6 its effect on SHMT is considerably greater. (3) Ineffective concentrations of AP/IMS agents become effective when combined with dB6. (4) The observed changes in SHMT activity are not, as one would expect, the same in the case of all four drugs. (5) The combination makes it possible to use much smaller doses of these agents with much better results, at least as far as the decrease of enzymic activity is concerned. This is very promising for clinical use of AP agents in cancer chemotherapy and IMS agents in transplantation especially of the heart and lungs, because combining these compounds with dB6 will make possible to use smaller doses over a longer period of time with greater effectiveness.