Correlation of ultrastructural and functional damage to mitochondria of ascites L1210 cells treated in vivo with methylglyoxal-bis(guanylhydrazone) or ethidium bromide.

摘要: Mitochondria of cultured L1210 leukemia cells undergo extensive swelling and structural disruption when exposed to the anticancer agent, methylglyoxal-bis(guanylhydrazone) (MGBG). Similar damage has now been observed in ascites treated vivo with a single dose (>50 mg/kg) either MGBG or ethidium bromide (EB). After 24 hr, mitochondria swell significantly, lose their inner structure, and, case EB treatment, develop numerous electron densities within matrix. Analysis ribonucleotide pools these by high-pressure liquid chromatography reveals that treatment depletes adenosine triphosphate markedly reduces overall adenylate energy charge cell. Thus, addition being structurally damaged, are functionally impaired both drugs. When MGBG-treated harvested, washed, placed untreated mice, all recover near normal ultrastructure after 48 whereas EB-treated do not, even 96 hr. indicates mitochondira have recovered functional capabilities as well. The for is essentially same cells. If allowed remain previously display unaltered leukemogenicity, killing animals at nearly average time significance contribution MGBG-induced mitochondrial antiproliferative action drug its relationship inhibition spermidine spermine biosynthesis remains be established.