Histological conformity of implantation tumors produced by kidney cell lines derived from dimethylnitrosamine-treated rats, with dimethylnitrosamine-induced renal mesenchymal tumors

The histology of five implantation tumors induced in rats by the deposition of cultured cell lines derived from dimethylnitrosamine (DMN)-treated rats is described and compared with the morphology of the predominant kidney neoplasm induced in vivo by a single high dose of DMN. The cell lines leading to growth upon implantation were long-established, continuously growing cultures obtained either from a DMN-induced renal mesenchymal tumor or from rats treated shortly before with a carcinogenic dose of DMN. The latter cultures had expressed morphological transformation at subcultures 5 or 6. All of the implantation tumors were of mesenchymal type, comprising variously a range of cell forms including fibroblast-like spindle cells, smooth muscle fibers, and "giant" cells, which resembled common aspects of the parent mesenchymal tumors induced in the rat kidney by DMN. Deposition of cells intrarenally illustrated the survival of remnants of preexisting nephrons as epithelial profiles scattered through the proliferating malignant tissue, a feature most characteristic of the parent tumor. The results confirmed the malignant nature of the various cell lines tested, in keeping with their altered behavior in vitro, and they were consistent also with the premise that the in vivo-in vitro system is selecting cells in culture that represent the same target population from which the renal mesenchymal tumors are derived in vivo.     

Development of experimental brain tumors in modulated amine metabolism]

There was found a correlation between dynamic changes in the serotonin level and mortality in rats with 9,10-dimethyl-1,2-benzanthracene induced blastomogenesis. An estimation was made of the influence of monoamine oxidase inhibitors, transamine and D, L-malic acid benzyldihydrazide on the type of a tumor produced. Chemical blastomogenesis in the case of cerebellar tumors is shown to be associated with the decreased serotonin content at the site of a tumor. But fluctuations of the serotonin level in the hypothalamus have not been detected. This evidenced that the decreased mortality rate caused by the administration of monoamine oxidase inhibitor is due to a lower production of astrocytomas and genetically related glioblastomas. The role of serotonin in increasing the astrocyte resistance to malignant degeneration has been discussed.     

Induction of free radicals and tumors in the kidneys of Wistar rats by ferric ethylenediamine-N,N'-diacetate

An iron chelate, ferric ethylenediamine-N,N’-diacetate[Fe(III)-EDDA], was found to produce hydroxyl radicals withhydrogen peroxide, as determined by both a deoxyribose degradationtest and electron spin resonance. Hydroxyl radical productionwas inhibited not only by adding hydroxyl radical scavengersand catalase, but also by adding superoxide dismutase to thereaction mixture, suggesting that superoxide anion may be involvedin the hydroxyl radical production. A single injection of Fe(III)-EDDA(10 mg Fe/kg body wt) to Wistar rats induced thiobarbituricacid reactivity in the kidneys and liver. Repeated Injectionsof Fe(III)-EDDA (10 mg Fe/kg body wt, twice weekly for 3 months)induced a 40% incidence of renal tumors, including renal adenocarcinomaand renal adenoma, 1 year later. These results suggest thatFe(III)-EDDA is an effective free radical producer in vitroand in vivo and that it may be useful in preparing animal modelsrelated to iron-dependent free radical damage. The results supportour hypothesis that endogenous or exogenous iron, complexedwith certain kinds of chelators, promotes free radical-dependenttissue damage and ultimately leads to carcinogenesis in theaffected tissue.     

Influence of immunodepressants on transplanted ovarian tumors in rats]

Under study was the effect of hydrocortisone injection and x-ray irradiation in a recipient on the development of a transplanted ovarian tumor in rats. The irradiation was shown to have a greater stimulating effect on the neoplastic growth than hydrocortisone.     

Induction of stomach tumors in rats by N-methyl-N-nitroso-N1-nitroguanidine]

N-methyl-N-nitroso-N'-nitroguanidine was administered as drinking water to Wistar strain and non-inbred male rats in the dosage of 100 mKg/ml for 7 months, Adenocarcinomas of the stomach were produced in about 70% of rats. The first tumors in the glandular stomach were noticed in 10-12.5 months. Studies of the kinetics of morphological changes indicated that MNNG induced a damage to the mucous membrane, subsequent regenerative hyperplasia, adenomatous hyperplasia with cellular and structural atypism, atrophy, pylorization of the mucosa and development of gastric adenocarcinomas.     

Ascorbic, keto and hydroxy acid metabolism in the cell nuclei of certain tumors]

The authors report the results of studies on the content of ascorbic acid, pyruvic acid and the activity of malate dehydrogenase decarboxylizing (MDHD) in cell nuclei of uterine fibromyoma, glandular hyperplasia of the endometrium with epithelial proliferation, common ovarian cyst and solid cancer. It was shown that due to the glycolysis inhibited respiration an oxidated form of ascorbic acid is absent in every case, whereas the MDHD activity is not manifested. The amount of a reduced form of ascorbic and pyruvic acid in benign tumors is at the control level, but in malignant growth these indices are markedly increased.     

Reduced transplantability of syngeneic tumors in rats immunized with allogeneic tumors

The growth of transplanted syngeneic tumors in Wistar/KA (WKA) rats was inhibited by three immunizations with tumors from allogeneic Donryu rats which possibly are unrelated antigenically. Inhibition of syngeneic tumor growth was not associated with the source or type of the tumors (carcinoma and sarcoma) used. A slight inhibition was also observed in rats immunized with a large amount of xenogeneic tumor or allogeneic normal spleen, liver and kidney cells. Inhibition was also observed after immunization with syngeneic tumors artificially infected with murine leukemia virus. However, the inhibition was strongest in rats immunized with allogeneic tumors. The mechanism of inhibition may be immunological, and it may be associated with an increase in the non-specific immunity of the host.     

Raising the sensitivity threshold of the hypothalamohypophyseal system to the homeostatic action of estrogens in rats with transplanted tumors]

Daily injections of 0.57 mKg of diethylstylboestrol-propionate in hemicastrated female rats inhibited the compensatory ovarian hypertrophy in control animals by 50%, and in rats with transplanted homologous fat-muscular tissue--by 4-%. In animals with subcutaneously transplanted Walker carcinoma-256, sarcome-45 and Pliss lymphosarcome this effect of estrogens was not manifested at all. The data obtained appear to evidence an increased threshold of sensitivity of the hypothalamol-hypophyseal system to a suppressing effect of estrogens in animals during the process of growth of transplantable tumors.     

The relationship between several biological properties of tumors and their metabolism]

Cytochemically, in smears-impressions of gastric and pulmonary tissue the authors studied alpha-glycerophosphate (a GPDH), succinate (SDH) and dihydroorthate (DDG) dehydrogenases that gives one an idea on the activity of energetic processes and initial stages of nucleic acid synthesis. It seems that a quantitative cytochemical analysis of the enzymic profile of tumor will allow some suggestions as to a capacity of tumors to metastasize and a degree of resistance to the therapy employed.