Independence of drug action on mitochondria and polyamines in L1210 leukemia cells treated with methylglyoxal-bis(guanylhydrazone).

摘要: The relationship between inhibition of polyamine biosynthesis and interference with mitochondrial structure function by the antitumor agent, methylglyoxal-bis(guanylhydrazone) (MGBG), was examined studying temporal sequence events relevant to these two drug actions. In ascites L1210 cells treated in vivo a single dose MGBG (75 mg/kg), significant pyruvate utilization, used here as measure function, occurred within 1 hr after initiation treatment continued decrease for 24 hr. Ultrastructural damage mitochondria, form swelling, first apparent 50% 6 > 90% 20 Inhibition S -adenosylmethionine decarboxylase, key enzyme spermidine spermine biosynthesis, treatment. Enzyme levels increased dramatically 8 result stabilization enzyme. Beginning at hr, ornithine responsible putrescine synthesis, slightly rise slowly during next 16 As consequence decarboxylase MGBG, intracellular pools began accumulate 2 rapidly 12 contrast, decreased 4 while even more slowly. However, amounts both polyamines were still present intracellularly. Since MGBG-induced changes precede alterations pools, it is concluded that effects are separable. This conclusion further supported finding that, cultured α-methylornithine concentrations which effectively inhibited ultrastructure unaffected. Results study raise possibility might be early antiproliferative action drug.