Comparisonof Specificityof Inhibitionof PolyamineSynthesisin BovineLymphocytesby EthylglyoxalBis(guanylhydrazone) and MethylglyoxalBis(guanylhydrazone)1

نویسندگان

  • Kazuei Igarashi
  • Carl W. Porter
  • David R. Morris
چکیده

Ethylglyoxal bis(guanylhydrazone) (EGBG) was compared as an inhibitor of polyamine biosynthesis with methylglyoxal bis(guanylhydrazone) (MGBG) in bovine small lymphocytes stim ulated by concanavalin A. EGBG brought about a decrease in spermidine and spermine levels equal to that found with MGBG, but at a 5-fold lower intracellular drug concentration. Despite identical polyamine levels, the degree of inhibition of DNA and protein synthesis by EGBG was smaller than that observed with MGBG, in either the presence or absence of the ornithine decarboxylase inhibitor, «-difluoromethylornithine. It was found that in vitro protein synthesis and in vivo mitochondria! function were inhibited by concentrations of MGBG necessary to inhibit polya mine synthesis in cells (1 to 3 mu), but not by efficacious levels of EGBG (0.2 to 0.6 HIM). These results suggest that EGBG is more suitable as a specific inhibitor of polyamine biosynthesis and that use of this drug, rather than MGBG, in combination with a-difluoromethylornithine may be useful for studying the physio logical functions of polyamines in animal cells.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Carcinostatic action of polycarbonyl compounds and their derivatives. III. Hydroxymethylglyoxal bis (guanylhydrazone).

The authors have previously noted the moder ate antileukemic effects of a-ketoaldehydes (2) and the considerably more potent antileukemic effects of glyoxal bis(guanylhydrazone) and methylglyoxal bis(guanylhydrazone) (1). These com pounds and closely related drugs were also studied as inhibitors of Adenocarcinoma 755. Preliminary investigation indicated that hydroxymethylglyoxal bis(guanylhydra...

متن کامل

Ultrastructural changes in the mitochondria of intestinal epithelium of rodents treated with methylglyoxal-bis(guanylhydrazone).

Ultrastructural studies of rats or mice treated for 24 hr with a toxic dose (100 mg/kg) of methylglyoxal-bis(guanylhydrazone) revealed the presence of damaged mitochondria in the crypt cells of the intestinal epithelium. Mitochondria were severely swollen and electron lucent, and appeared to be similar to those observed previously in a variety of cell types treated in vitro and in vivo with met...

متن کامل

Effects of 4,4'-diacetyl-diphenyl-urea-bis(guanylhydrazone) on leukemia L1210.

A new aromatic bisguanylhydrazone derivative, 4,4'-diacetyldiphenyl-urea-bis(guanylhydrazone), markedly prolonged the survival of DBA/2Ha and DBA/2J mice inoculated i.p. or s.c. with leukemia L1210. Drug-induced 50-day cures of leukemic mice occurred with a higher incidence in DBA/2Ha than in DBA/2J mice, and in female than in male mice. The drug was active by parenteral but not by oral route o...

متن کامل

Inhibition of S-adenosylmethionine decarboxylase and diamine oxidase activities by analogues of methylglyoxal bis(guanylhydrazone) and their cellular uptake during lymphocyte activation.

Several congeners of methylglyoxal bis(guanylhydrazone) were tested for their ability to inhibit eukaryotic putrescine-activated S-adenosylmethionine decarboxylase (EC 4.1.1.50) and intestinal diamine oxidase (EC 1.4.3.6). All the compounds tested, namely methylglyoxal bis(guanylhydrazone), ethylglyoxal bis(guanylhydrazone), dimethylglyoxal bis(guanylhydrazone) and the di-N"-methyl derivative o...

متن کامل

Non-p-glycoprotein-mediated multidrug resistance in detransformed rat cells selected for resistance to methylglyoxal bis(guanylhydrazone).

Three independent variants (G2, G4, G5), resistant to methylglyoxal bis(guanylhydrazone), an anticancer drug, have been isolated by single step selection from an adenovirus-transformed rat brain cell line (1). These variants display selective cross-resistance to several natural product drugs of dissimilar structure and action. Multidrug resistance has recently been shown to be caused by overexp...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2006