Alhonen-Hongisto L, Fagerström R, Laine R, Elo H, Jänne J
Biochem J. 1984 Jul 1;221(1):273-6. doi: 10.1042/bj2210273.
Three bis(guanylhydrazones) (those of methylglyoxal, glyoxal and ethylglyoxal) were compared for their affinity for the putative polyamine carrier and for their cellular retention in L1210 mouse leukaemia cells. All the bis(guanylhydrazones) inhibited equally effectively the uptake of spermidine by the tumour cells, indicating that the compounds had roughly equal affinity for the polyamine carrier. The fact that methylglyoxal bis(guanylhydrazone) and glyoxal bis(guanylhydrazone) were much more effectively concentrated in the animal cells than was ethylglyoxal bis(guanylhydrazone) was obviously attributable to the finding that the efflux rate of ethylglyoxal bis(guanylhydrazone) greatly exceeded that of the other bis(guanylhydrazones). The rate of efflux of the drugs was slowed down if the tumour cells were treated with 2-difluoromethylornithine before exposure to the bis(guanylhydrazones). These results suggest that intracellular binding of the bis(guanylhydrazones) determines their cellular accumulation.
比较了三种双（胍腙）（甲基乙二醛、乙二醛和乙基乙二醛的双（胍腙））对假定的多胺载体的亲和力及其在L1210小鼠白血病细胞中的细胞滞留情况。所有双（胍腙）对肿瘤细胞摄取亚精胺的抑制效果相同，表明这些化合物对多胺载体的亲和力大致相等。甲基乙二醛双（胍腙）和乙二醛双（胍腙）在动物细胞中的浓缩效果比乙基乙二醛双（胍腙）有效得多，这一事实显然归因于乙基乙二醛双（胍腙）的外排速率大大超过其他双（胍腙）。如果在暴露于双（胍腙）之前用2-二氟甲基鸟氨酸处理肿瘤细胞，药物的外排速率会减慢。这些结果表明，双（胍腙）的细胞内结合决定了它们在细胞内的积累。
