Flux of free fatty acids among host tissues, ascites fluid, and Ehrlich ascites carcinoma cells

The role of plasma free fatty acids (FFA) in the transport of fatty acids from host tissues to Ehrlich ascites carcinoma in mice was studied. [9,10-(3)H] Palmitate complexed to mouse serum (albumin) was injected either intraperitoneally or intravenously into unanesthetized tumor-bearing mice. The incorporation of radioactivity into tumor extracellular fluid FFA, tumor cell FFA, neutral lipid, phospholipid, water-soluble material in cells and fluid, plasma FFA, host carcass total lipid fatty acids, and water-soluble (i.e., nonlipid) material was measured. In addition, the quantity of fatty acid in each of the above lipid fractions was determined. The data were analyzed by multicompartmental analysis (SAAM) using a digital computer, and fractional rate constants of FA movement within and out of the host-tumor system were calculated. These rate constants and pool size measurements were used to estimate the corresponding fluxes. Although FFA in the tumor's extracellular fluid were replaced rapidly, almost none of the newly formed fluid FFA was derived from plasma FFA. Moreover, the transfer of FFA from the tumor extracellular fluid FFA to plasma FFA was virtually negligible. We suggest that the net amount of FFA required to replace the fluid FFA utilized for tumor energy and growth may be derived from direct transfer of FFA from host tissues to the ascitic fluid and that plasma FFA is not an intermediate in this transport process. The transport of FFA from the host to tumor cell lipids through the tumor extracellular fluid was about 26-fold greater than that required to account for net lipid accumulation during growth.     

Zinc-, copper- and cadmium-binding protein in Ehrlich ascites tumour cells.

The properties of Ehrlich ascites tumour cells exposed in vivo to cadmium were investigated as a function of the zinc status of the host animals. Tumour-cell growth was inhibited by cadmium in both zinc-sufficient and zinc-deficient animals. However, cells in zinc-sufficient tumours accumulate much less cadmium than those in deficient tumours. The subcellular distributions of cadmium and zinc do not depend on zinc status. Cadmium and zinc are bound to a low-molecular-weight protein with properties similar to metallothionein. Without exposure to cadmium, a zinc- and copper-binding protein is still present that behaves like a metallothionein. This protein can rapidly bind cadmium added to Ehrlich cells in vitro. It is shown that the zinc- and copper-binding protein contains free thiol groups. Ehrlich cells isolated from cadmium-treated animals are viable and show normal incorporation of uridine into RNA, but the cellular uptake of thymidine and its incorporation into DNA are inhibited.     

Impact of acute ascites on the action of the canine abdominal muscles.

Although ascites causes abdominal expansion, its effects on abdominal muscle function are uncertain. In the present study, progressively increasing ascites was induced in supine anesthetized dogs, and the changes in abdominal (DeltaPab) and airway opening (DeltaPao) pressure obtained during stimulation of the internal oblique and transversus abdominis muscles were measured; the changes in internal oblique muscle length were also measured. As ascites increased from 0 to 100 ml/kg body wt, Pab and muscle length during relaxation increased. DeltaPab also showed a threefold increase (P < 0.001). However, DeltaPao decreased (P < 0.001). When ascites increased further to 200 ml/kg, resting muscle length continued to increase and muscle shortening during stimulation became very small so that active muscle length was 155% of the resting muscle length in the control condition. Concomitantly, DeltaPab returned to the control value, and DeltaPao continued to decrease. Similar results were obtained with the animals in the head-up posture, although the decrease in DeltaPao appeared only when ascites was greater than 125 ml/kg. It is concluded that 1) ascites adversely affects the expiratory action of the abdominal muscles on the lung; 2) this effect results primarily from the increase in diaphragm elastance; and 3) when ascites is severe, the abdomen cross-sectional area is also increased and the abdominal muscles are excessively lengthened so that their active pressure-generating ability itself is reduced.     

Prune belly syndrome and fetal ascites.

A case of prune belly syndrome (PBS) in a 22 week male fetus is described. All the features characteristic of the syndrome were present: absence of abdominal muscle; dilatation of the bladder, ureters, and renal pelves; and undescended testes. In addition, there was marked ascites. The rectus abdominis muscles were entirely absent whereas other abdominal muscles were only absent centrally. Between regions of normal and absent musculature muscle fibers were sparse, enlarged, frequently disrupted, and mostly in the myotubule stage. The prostate was thin-walled and its urethra greatly expanded. The testes lay close to the corresponding ureters and each ductus deferens was only partially present. It is considered that prostatic dysgenesis and fetal ascites are key factors in the causation of PBS.     

Characterization of the Ehrlich ascites tumor plasma lipoproteins.

1. The lipoproteins of the Ehrlich ascites tumor plasma were separated into 3 distinct fractions, very low density, low density and high density lipoproteins by preparative ultracentrifugation combined with agarose column chromatography. 2. High density lipoproteins contained 74% of the total protein in the lipoproteins. By contrast, most of the lipids were present in the very low density lipoprotein fraction. 3. The fatty acid compositions of the cholesteryl esters were appreciably different in the very low, low and high density lipoproteins, whereas phospholipid and triacylglycerol fatty acid compositions were quite similar in the 3 lipoprotein fractions. 4. Very low and high density apoprotein electrophoretic patterns on sodium dodecyl sulfate-acrylamide gels were similar to those observed in the corresponding lipoprotein fractions obtained from other mammalian species. The low density fraction, however, contained 7 apoprotein bands, and 32% of the low density apoprotein was soluble in tetramethyl urea. 5. The average molecular weights as determined by analytical ultracentrifugation were 2-10(7) (very low density), 6-10(6) (low density) and 4.4-10(5) (high density).     

Interference of MHV3 virus on ascites tumor growth.

In this experimental study the Authors have evaluated the interference of MHV3 hepatitis virus on Ascites Tumor's growth, using 4 groups of mice, the first one considered as control, the others inoculated with the virus 48 hours before, at the same time and 48 hours after tumor's inoculation. In each group labeling index, mitotic index and ascites volume were assessed a week after tumor's inoculation. The results seem to reveal an inhibition of tumor's growth in the second group. For this reason on the base of these encouraging observation, the Authors will continue researches to further confirm these preliminary results.     

Pepstatin, an inhibitor of acid kininogenases and ascites retardant in neoplastic disease.

Evidence is reviewed that pepstatin, an inhibitor of acid kininogenases such as cathepsin D, may be an effective therapeutic agent in retarding ascites accumulation in certain cancers. The evidence for this conclusion is based on the actions of pepstatin in retarding ascites in six different tumor strains inoculated into various species of mice, as well as the demonstration that cathepsin D activity is reduced in vivo in several organs following pepstatin administration. The latter is significant since we have postulated that ascites formation, in good part, is due to leukokinin formation, which is catalyzed by cellular-released cathepsin D.