Adenomatous changes, and early and invasive carcinomas of the glandular stomach in Wistar rats ingesting N-methyl-N'-nitro-N-nitrosoguanidine were studied. Almost all adenomatous changes and carcinomata were located near the midpoint of the lesser curvature. In electron microscopic and histochemical studies, both changes showed great cytological similarity. Electron microscopically, they were found to consist of predominantly undifferentiated cells with poorly developed cytoplasmic organelles, with some highly differentiated cells present. Histochemically, both showed strongly positive reactions for lysosomal enzymes. For tumor transplantation, five lesions were used and in all cases, the transplants were successful.

A highly sensitive method for the immuno-histochemical localisation of carcinoembryonic antigen (CEA) is described. This method is based on the binding of a peroxidase-antiperoxidase complex (PAP) to anti-CEA antibodies by means of an anti-gamma-globulin which reacts with both the anti-CEA and the antiperoxidase antibodies. Using the technique described here, CEA was localised in conventionally processed normal and cancerous colonic tissue. In normal as well as in neoplastic tissues, a CEA-specific staining of cell membranes and cytoplasm was demonstrated. In frozen sections of normal colonic tissue CEA was found even at high dilutions of the first antibody; this indicates the high sensitivity of the method. The applicability of the method to conventionally processed and thereby well preserved tissue specimens opens the possibility to identify CEA by light microscopy even at very low concentrations.

To examine the significance of anti-catabolism in renal hypertrophy, cellular autophagy was investigated by electron microscopic morphometry in proximal tubular cells (PTCs) of the outer cortex of the rat kidney after the induction of diabetes mellitus by streptozotocin (STZ) and after unilateral nephrectomy. Adult male Sprague-Dawley rats were divided into three groups and killed by retrograde perfusion fixation, 1, 2 and 3 days after the induction of diabetes (group D; n = 24), after unilateral nephrectomy (group N; n = 24) and after combined treatment (group DN; n=24). Untreated, agematched litter mates served as controls (group C; n = 24). By comparison with these controls, the left kidney to initial body weight ratio was increased by 8, 23, and 15% in group D animals, by 8, 23, and 24% in group N animals, and by 10, 21, and 25% in group DN animals at the first, second and third day, respectively. Quantitative evaluation of large test areas showed that the volume and numerical densities of autophagic vacuoles (AVs) in PTCs were significantly lower in these hypertrophed kidneys than in the controls. The average reduction in AV volume density was about 65% in group D animals, about 50% in group N animals and about 75% in group DN animals. These data show that autophagic degradation of cytoplasmic components in PTCs is inhibited in renal hypertrophy independently of the growth stimulus, i.e. uninephrectomy or diabetes. Since insulin per se inhibits cellular autophagy in PTCs, the expected effect of insulin dificiency seems to be counteracted by as yet undefined stimuli that may be related to metabolic work load.

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Five monoclonal antibodies that recognize different epitopes on carcinoembryonic antigen (CEA) were reacted with tissue sections of various carcinoma specimens. The vital, non-necrotic tissues of those carcinomas of the oesophagus, pancreas, colon and rectum, medullary thyroid, ovary and cervix in which CEA related epitopes were detectable bound all five antibodies to a similar degree. In 3/5 lung carcinomas, 2/10 mammary carcinomas and 1/5 gastric carcinomas, a significantly different binding of the monoclonal antibodies by vital tumour tissue was present as determined by three independent investigators. In necrotic tissue areas, heterogeneity of antibody binding was more common. In a previous investigation, it was shown that normal granulocytes and liver tissue differentially bind the monoclonal anti-CEA antibodies, indicating the presence of crossreacting antigens. The equivalent binding of the five monoclonal anti-CEA antibodies to most of the carcinomas tested suggests that this binding is due to the presence of complete CEA molecules and not only of cross-reacting antigens.