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Morphological evidence for an antimitochondrial action by methylglyoxal-bis(guanylhydrazone).

Exposure of cultured leukemia L1210 cells to 0.1 micron methylglyoxal-bis(guanylhydrazone) resulted in a concentration-dependent inhibition of cellular proliferation, beginning after about 1 to 2 generation times (12 to 24 hr). Ultrastructural examination of the cells treated at and above 1.0 micron concentrations of drug for 24 hr revealed unifrom damage to mitochondria. The basic lesion involved extensive swelling of the mitochondrion, a deterioration and eventual loss of cristae, and a decrease in the matrix density. This damage preceded growth inhibition by about 12 hr and did not immediately affect cell viability as detected by trypan blue dye exclusion. Whether these findings are related to the known actions of the drug on polyamine metabolism is not clear at present.