Carcinogenicity in mice of some fatty acid methyl esters. 2. Peroral and subcutaneous application.

Two fatty acid methyl esters, methyl oleate and methyl 12-oxo-trans-10-octadecenoate, have been tested for carcinogenicty by oral and subcutaneous administration in ST/a mice of both sexes. A positive effect of methyl oleate could not be assessed, while the results pointed to a promoter effect of methyl oxo-octadecenoate. Given in the diet, this compound increased the incidence and number of forestomach papillomas within 83 weeks after initiation by 4-nitroguinoline 1-oxide. Repeated injections of methyl oxo-octadecenoate in the inguinal area resulted in 2 local sarcomas in a group of 20 females which had previously received skin initiation by 7, 12-dimethylbenz [alpha] anthracene in the neck. In no other animal group did sarcomas appear at this location within the observation period of 2 years. An influence by the injected methyl esters on the initiated skin carcinogenesis was possibly, but weakly, present. The need for more extensive experiments is stressed, especially with a view to the possible carcinogenic hazards involved in dietary intake of oxygen-containing derivatives of oleic acid.

Role of C'3 and Fc receptors in B-lymphocyte activation.

Attempts were made to identify the non-Ig lymphocyte receptor responsible for B-cell induction by antigen and polyclonal B-cell activators (PBA). As a first step, the role of C'3 and Fc receptors was analyzed. It was shown that complement could be fixed onto B cells to such an extent that the lymphocytes could not bind complement-coated red cells, but this did not result in induction of polyclonal antibody synthesis, nor did it inhibit the lymphocytes response to PBA. However, the C'3 receptros possessed a passive focussing role in the induction of polyclonal antibody responses. Thus, PBA that had fixed complement activated polyclonal responses at lower concentrations than the same substances that had not fixed complement. Most likely the dual binding of PBA molecules to B cells by the PBA and the C'3 receptors caused more PBA molecules to be bound to each cell. However, the focussing function of the C'3 receptors was several orders of magnitude smaller than that of the Ig receptors. Analogous studies were carried out with Fc receptors. Binding of different types of antigen-antibody complexes did not cause activation of polyclonal or specific antibody synthesis, nor did it significantly interfere with induction of antibody synthesis by PBA substances.

The interaction of cationic liposomes containing entrapped horseradish peroxidase with cells in culture.

Cationic liposomes composed of sphingomyelin, cholesterol, and stearylamine were prepared with horseradish peroxidase trapped inside. Stable particles were formed in which 10-12% of the enzymic activity appeared to be located at, or near, the outer surface of the liposome. Adsorption and uptake of liposomes by HeLa cells were followed cytochemically by electron microscopy and quantitated by enzyme assay and by the distribution and fate of particles labeled with [(14)C]cholesterol and [(125)I]horseradish peroxidase. The particles were adsorbed by HeLa cells at least 300 times as efficiently as was free horseradish peroxidase. Many of the particles remained at the cell surface, but numerous membrane-bound cytoplasmic inclusions were observed to contain peroxidase-staining material. In addition, many areas of the cell membrane gave a positive staining reaction. It was concluded that many particles (presumably the larger ones) did not gain access to the interior of the cells, many were phagocytized, and some enzyme was transferred to the cell membrane, perhaps as a result of fusion of the liposomal membrane with the cell membrane.

Incidence and significance of faecal hydroxystearic acid in alimentary disease.

Three-day faecal collections were obtained from 87 patients with a variety of gastroenterological diagnoses and 12 control subjects while consuming normal diets. Faecal weight, total fatty acids, and the proportion of hydroxystearic (OHSA) acid were measured. All patients had some easily detectable hydroxystearic acid. It was found that in general the percentage of OHSA in the faecal fatty acids increased with increasing fat output. Thus most patients excreting less than 20 g of fat per day had less than 5% OHSA while those with greater steatorrhoea had levels of 6 to 23%. Exceptions were patients with mild steatorrhoea with ileal disease, ileal resections, or small intestinal bacterial colonization, who had more than 5% OHSA whilst patients with colonic resection had much lower levels of OHSA than otherwise found. It is impossible to determine whether OHSA had a specific cathartic action from this study since the data implicated total fatty acids to the same extent.