MORPHOLOGICAL EVIDENCE FOR AN ANTI-MITOCHONDRIAL ACTION BY METHYLGLYOXAL-BIS(GUANYLHYDRAZONE)

Abstract

Exposure of cultured [mouse] leukemia L1210 cells to 0.1-10 .mu.M methylglyoxal-bis(guanylhydrazone) resulted in a concentration dependent inhibition of cellular proliferation, beginning after .apprx. 1-2 generation times (12-24 h). Ultrastructural examination of the cells treated at and above 1.0 .mu.M concentrations of drug for 24 h revealed uniform 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 .apprx. 12 h and did not immediately affect cell viability as detected by trypan blue exclusion. Whether these findings are related to the known actions of the drug on polyamine metabolism is not clear at present.