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 G₂ 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 procylics. Furthermore, these short-stumpy forms exhibit α-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.