Biomedical subjects

J G Delcros

Publications and source records attributed to J G Delcros.

40 records · Page 3Linked to original sources

PubMed1984

The competitive inhibition of tissue transglutaminase by alpha-difluoromethylornithine.

The transglutaminase-mediated insertion of putrescine into casein was inhibited competitively by alpha-difluoromethylornithine (alpha-DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase. Preincubation of the amine acceptor (casein) or the enzyme itself with the inhibitor did not affect enzyme activity. Alpha-DFMO is a poorer substrate for transglutaminase (Km = 2.10 mM) than putrescine (Km = 0.17 mM). The inhibitory effect was also found with fibronectin as amine acceptor.

Acyltransferases↗

PubMedDate not supplied

Dimethylsilane polyamines: cytostatic compounds with potentials as anticancer drugs. II. Uptake and potential cytotoxic mechanisms.

Dimethylsilane tetramines are structural analogues of spermine with a (CH3)2 Si-group incorporated into the central carbon chain. They have potential as anticancer drugs. Their cytotoxic effect was considered to rely mainly on their polyamine antagonist property. In order to obtain new ideas about cellular mechanisms, which are potential targets of the dimethylsilane polyamines, the effects of these compounds on some basic cell functions, such as protein and DNA synthesis, and calmodulin antagonism were studied. In addition, their mode of accumulation in cells was investigated. It became evident that the intracellular accumulation of dimethylsilane polyamines is almost exclusively achieved via the polyamine transport system. However, the exchange of a part of the intracellular natural polyamines against dimethylsilane polyamines has only a small effect on polyamine uptake. Binding to the endoplasmic reticulum and inhibition of protein synthesis are presumably important for the cytotoxic action of bis(11-amino-4,8-diazaundecyl)dimethylsilane, a hexamine, but seem of no importance for the tetramines. Calmodulin antagonism, however, is likely to contribute to their cytotoxic effect.

Animals↗

PubMedDate not supplied

Spermidine uptake by erythrocytes from normal and Lewis lung carcinoma (3LL) grafted mice: I. In vitro study.

High red blood cell (RBC) spermidine levels have been observed in patients harboring various histological types of cancer. In an attempt to explain the mechanism of RBC spermidine uptake in the malignant cell growth process, erythrocytes from normal and (3LL) Lewis lung carcinoma grafted mice were incubated with [14C] spermidine in the presence of PBS or plasma from normal or 3LL grafted mice. Though RBC of cancer mice harbor abnormally elevated spermidine concentrations as compared with those of controls, when incubated with PBS, 3LL grafted mice exhibit [14C] spermidine uptake three times higher than that of normal mice erythrocytes in the same incubating conditions. Moreover, if plasma incubations always increase spermidine uptake in RBC from cancer mice compared with erythrocytes only incubated with PBS, plasma incubations are responsible for two opposite effects in RBC of normal mice: plasma increases spermidine uptake in PBS unwashed erythrocytes and lowers it in PBS washed RBC. One possible explanation for the observed plasma stimulating effect in RBC spermidine uptake might be the presence of a plasma component common to plasma from normal and cancer mice, able to interact with RBC membrane proteins. In erythrocytes from cancer mice, the high spermidine concentration would be responsible for the observed compactness in band 3 proteins involved in ionic transport through RBC stroma. In normal mice erythrocytes which exhibit low polyamine levels, the observed dissociation of band 3 proteins might explain the spermidine uptake in PBS washed normal RBC incubated with plasma. In vivo, this plasma component would participate in the stabilization of normal mice membrane proteins involved in RBC spermidine uptake.

Animals↗

PubMedDate not supplied

Accumulation of hydroxyspermidine in red blood cells, a potential index of tumor proliferation rate.

It has previously been demonstrated that during Lewis Lung carcinoma growth, red blood cell spermidine levels increase concomitantly with tumor volume. If [14C] putrescine or 2-methylputrescine are administered, [14C] spermidine and methylspermidine, respectively, accumulate in red blood cells in proportion with the tumor volume. In the present work the metabolic transformation of 2-hydroxyputrescine, a natural derivative of putrescine, to hydroxyspermidine, was studied in tumor bearing mice. After a single i.p. injection of 2-hydroxyputrescine, higher concentrations of hydroxyspermidine were found in the tumor than in liver. In the red blood cells of Lewis lung carcinoma-bearing mice, hydroxyspermidine was detected between 24 hours and 96 hours after i.p. injection of 2-hydroxyputrescine. The concentration of hydroxyspermidine found in red blood cells was proportional to the tumor volume. Hydroxyspermidine has potential as a marker of malignant cell proliferation in human oncology.

Animals↗