THE EFFECTS OF THE METHYLATING AGENT 1,2-BIS(METHYLSULFONYL)-1-METHYLHYDRAZINE ON MORPHOLOGY, DNA CONTENT AND MITOCHONDRIAL-FUNCTION OF TRYPANOSOMA-BRUCEI SUBSPECIES

Repeated exposure of trypanosomes in vitro or in vivo to low concentrations of the methylating agent 1,2-bis(methylsulfonyl)- 1 -methylhydrazine induces a series of moderately synchronous morphological and biochemical changes. Cell division halts and the long-slender bloodstream forms transform to short-stumpy forms via larger intermediate-stage cells which contain approximately double the normal G, content of DNA. In common with naturally occurring short-stumpy trypanosomes, drug-induced short-stumpy forms do not infect rodents and when transferred to Cunningham's medium, transform to and replicate as procyclics. Furthermore, these short-stumpy forms exhibit alpha-ketoglutarate supported motility and oxygen consumption, acquire the ability to reduce nitroblue tetrazolium (NADH diaphorase positivity) and appear to be in the G1 or G0 stage of the cell cycle based upon DNA content.