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B Knödgen

Publications and source records attributed to B Knödgen.

32 records · Page 2Linked to original sources
PubMed1981

UV-induced changes in urinary polyamine excretion in the mouse.

Exposure of hairless mice to the light of a germicidal lamp (254 nm) under conditions which are known to induce epidermal DNA synthesis, cell proliferation, and polyamine metabolism produced a marked increase of polyamine excretion in the urine which lasted for many days. The increase was about the same for free and acetylated polyamines. Although the ratio of N1-acetylspermidine/N8-acetylspermidine increased somewhat in the urine of animals exposed to UV, the increase was not significant enough to be useful as a marker of enhanced cell proliferation. A single topical dose of alpha-difluoromethylornithine, a selective inhibitor or ornithine decarboxylase, prevented the UV-induced increase of polyamine excretion in agreement with its effect on UV-induced epidermal polyamine turnover.

Acetylation↗
PubMed1981

Metabolism of acetyl derivatives of polyamines in cultured polyamine-deficient rat hepatoma cells.

The acetyl derivatives of polyamines, N1-acetylspermine (N1-AcSPM) and N1-acetylspermidine (N1-AcSPD), are in vitro better substrates of tissue polyamine oxidase than the corresponding non-acetylated polyamines. Rat hepatoma tissue culture (HTC) cells, depleted of their putrescine (PUT) and spermidine (SPD) content by the use of DL-alpha-difluoromethylornithine (DFMeOrn), an irreversible inhibitor of L-ornithine decarboxylase, were used to study in situ the catabolism of these acetyl derivatives of polyamines. Normal intracellular spermidine content was restored by the addition of N1-acetylspermidine to polyamine-deficient cells. Addition of spermine (SPM) did not restore the spermidine content, although this polyamine elevated the spermine content of the cells. N1-Acetylspermidine reestablished normal spermidine levels of the cells and elevated the cellular putrescine content more efficiently and more rapidly than spermidine. Monoacetylputrescine and N1, N12-diacetylspermine (di-AcSPM) were ineffective in restoring putrescine and spermidine contents. These findings support the concept that N1-acetylspermine and N1-acetylspermidine are natural substrates of tissue polyamine oxidase and suggest poor membrane permeability of monoacetylputrescine (AcPUT) and N1, N12-diacetylspermine. Furthermore, they indicate that acetylation of polyamines by the cytosolic acetyl CoA: polyamine N1-acetyltransferase is the rate-limiting step of polyamine catabolism in rat hepatoma cells. Growth inhibition by DL-alpha-difluoromethylornithine was reversed by N1-acetylspermine and N1-acetylspermidine but not by monoacetylputrescine and N1, N12-diacetylspermine. These results suggest again that the antiproliferative effect of DL-alpha-dilfuoromethylornithine is related to inhibition of polyamine biosynthesis.

Acetylation↗
PubMed1980

Acetylation of spermidine in polyamine catabolism.

Treatment with thioacetamide (150 mg/kg) was used to enhance polyamine metabolism in rat liver. The increased uptake and catabolism of [14C]spermine and the changes of putrescine, spermidine and spermine concentrations indicated enhanced polyamine turnover rates. The increase of hepatic putrescine concentration was accompanied by an increase of monoacetylputrescine and N1-monoacetylspermidine concentration. In control animals, the latter compound was below detection levels. Thioacetamide treatment also enhanced putrescine excretion, which again was concomitant with an increased excretion of N1-acetylspermidine. The close time-dependent correlation between induced putrescine formation and enhanced formation of N1-acetylspermidine at a time when liver spermidine and spermine concentrations are not changed, favors the notion that acetylation is an essential step in polyamine degradation and elimination. The increase of polyamine oxidase and decrease of acetylpolyamine deacetylase activities in the liver of thioacetamide-treated rats is in line with an increased polyamine turnover, but these enzymes, although essential, are not rate-limiting in the catabolic reactions.

Acetamides↗
PubMed1980

Polyamine oxidase in rat tissues.

An assay procedure for polyamine oxidase in tissue homogenates was devised. The method is based on the degradation of N1,n12-diacetylspermine to N1-acetylspermidine and the determination using TLC of the latter. Polyamine oxidase activity is high in most tissues. Its activity is comparable to that of spermidine and spermine synthase. The independence of this enzyme from cellular proliferation rates and its relatively long biological half-life are indicative of a passive role of polyamine oxidase in the regulation of cellular polyamine levels.

Age Factors↗
PubMed1979

Determination of the naturally occurring monoacetyl derivatives of di- and polyamines.

A method is described for the determination of pmol quantities of monoacetylputrescine, N1-acetylspermidine, N8-acetylspermidine and related compounds. The method is based on the derivation of these compounds with 5-dimethylaminonaphthalene-1-sulphonylchloride, followed by thin-layer chromatographic separation. Cleanup steps allow the application of the method to urine analyses. From the repeated determination of acetylated polyamines in the urine of healthy individuals it can be concluded that these conjugates are the major excretory form of di- and polyamines. The cleanup steps used in this procedure and the method described for the stabilization of 5-dimethylaminonaphthalene-1-sulphonyl derivatives on thin-layer plates are advantageous also for the analyses of total polyamines in urine hydrolysates, and in related applications of the dansylation method.

Adult↗
PubMed1978

Determination of di-and polyamines by high-performance liquid chromatographic separation of their 5-dimethylaminonaphthalene-1-sulfonyl derivatives.

Using a Lichrosorb RP-8 reversed-phase column and a methanol--water gradient elution program, it is possible to separate within 40 min and to determine routinely in picomole quantities the natural di- and polyamines. The precision of the method is comparable to the thin-layer chromatographic procedures, the separations are most efficient, and the method can be fully automated. A modified gradient enables the repeated assay of spermidine and spermine within 20 min. The method is suited for polyamine analyses in tissues and body fluids.

Animals↗
PubMedDate not supplied

Polyamine deprivation, malnutrition and tumor growth.

Feeding an artificial, essentially polyamine-free diet which contained antibiotics for the decontamination of the gastrointestinal tract and 2-(difluoromethyl)ornithine (DFMO) and N,N'-bis-(2,3-butadienyl)putrescine for the inactivation of ornithine decarboxylase and polyamine oxidase, respectively, retarded the growth of several solid tumors by about 80%. In the present work the contribution of the major components of the treatment were analysed, using Lewis lung carcinoma growing in the hind leg of female C57BL mice. In addition to polyamine deprivation, malnutrition due to decreased food intake turned out to contribute significantly to tumor growth retardation. Ornithine decarboxylase was shown to be incompletely inhibited by administration of DFMO with the diet. A considerable improvement of polyamine deprivation can be expected from the continuous administration of this drug, or from analogous inhibitors with more favourable enzyme- and pharmaco-kinetic properties.

Animals↗
PubMedDate not supplied

Polyamine metabolism and polyamine excretion in normal and tumor bearing rodents.

Aminoguanidine sulfate (AG) inhibits in vivo oxidative deaminations of the polyamines and their derivatives. This compound was used to study urinary polyamine excretion by normal, and tumor bearing rodents. Of the total expendable polyamines, 64 percent were catabolized by AG-sensitive oxidases and escaped observation. Tumor bearing animals did not excrete enhanced amounts of polyamines at any stage of tumoral growth. However, treatment with adriamycin caused an increased polyamine excretion. Prolonged administration of a 2% solution of a-difluoromethylornithine (DFMO), reduced urinary polyamine excretion to the same level of about 27%, irrespective whether the animals carried a large tumor or not. Cadaverine excretion was not affected by treatment with DFMO. Based on these animal data, it appears that urinary polyamines are of restricted value in the diagnosis of tumors.

9,10-Dimethyl-1,2-benzanthracene↗