BIOCHEMICAL EFFECT OF PLANT GROWTH REGULATOR, N⁶-METHLADENINE, ON TRYPANOSOMID FLAGELLATES

Observations that plants produce chemicals that promote cell division were documented as long ago as 1892 (25) and were later reaffirmed by the research of Haberlandt in 1913 (8) who demonstrated that diffusates from phloem could elicit cell division in potato parenchyma.

The original name "kinin" for plant cell-division promoters conflicted with the same name used in animal biochemistry. The term cytokinin is now officially accepted for compounds that promote cytokinesis in plant cells. Cytokinin is defined as a compound that, in the presence of auxin, induces cell division in a suitable assay material grown in a defined media.

N⁶-methyladenine (6-methylaminopurine [6-MA]), a plant growth regulator and a normal constituent of nucleic acids, has been found to inhibit the growth of Trypa- nosoma cruzi, Leishmania braziliensis, L. donovani, L. tarentolae, L. mexicana, and Crithidia fasciculata. The extent of growth inhibition in these organisms is related to the sensitivity of guanine deaminase (guanine aminohydrolase, EC 3.5.4.3), adenine deaminase (adenine aminohydrolase, EC 3.5.4.2), and adenosine hydrolase and phosphorylase. 6-MA was not an inhibitor of the purine phosphoribosyltransferases. Of the trypanosomid flagellates tested, Trypanosoma cruzi was most susceptible to 6-MA. Neither adenine deaminase (as found in the leishmaniae and C. fasciculata) nor adenosine deaminase (as found in mammalian cells) could be demonstrated in T. cruzi. Guanine deaminase, which is strikingly inhibited by 6-MA in T. cruzi, appears to play a major role in the purine salvage pathway of this organisms as judged from growth experiments and enzyme inhibition studies. Enzyme sensitivities to 6-MA vary greatly depending upon the organism. Rabbit liver guanine deaminase was shown to be insensitive to 6-MA at the concentrations used in this study.