SINCE the classical investigations of Warburg, Posener and Negelein (1924) on the glycolytic processes in cancer tissues, the studies dealing with changes of enzymatic processes in relation to cancer have been numerous and are the subject of several reviews, (e.g. Greenstein, 1954; Fishman, 1959). The material studied varies from whole animals to subcellular particles and the significance attributed to the findings differs from causative connection to chance association. Numerous attempts have been made to use the enzymatic changes found in the blood and in the tissues of patients suffering from malignant tumours for diagnostic or prognostic purposes. As the knowledge of the chemistry and morphology of the cellular processes increases, the explanation for the changes of enzymatic processes in tumor cells is modified.The present investigations deal with the effect of the carcinogens dimethyl (DMN) and diethyl (DEN) nitrosamine on the ,3-glucuronidase and lactic dehydrogenase (LDH) activities during the development of tumors in rats. The comparative carcinogenic effect of these substances in the rat has been studied previously (Argus and Hoch-Ligeti, 1961). Changes caused by a carcinogen in the cytoplasmic protein molecules, either directly or consecutive to alteration of template nucleic acids, might manifest themselves in changes of enzyme activities. Methylation of proteins in rat liver slices during incubation with DMN has been described (Magee and Hultin, 1962). With the aid of DMN labelled with radioactive carbon, incorporation of the label into the deoxyribonucleic acid of the liver and probably also of the kidney has been demonstrated. Acid hydrolysis of labelled ribonucleic acid from the liver yielded a 7-methylguanine (Magee and Farber, 1962). The carcinogenic activity of nitrosamine derivatives was thought to be related to protein denaturation (Argus, Leutze and Kane, 1961) or to methylation of sulfhydryl groups in amino acids (Schoental, 1961).The enzyme systems ,8-glucuronidase and LDH were selected for the present study because of their different intracellular distribution. /3-glucuronidase is largely localized in the lysosomes (deDuve, Pressman, Gianetto, Wattiaux and Appelmans, 1955) and, if the intracellular membranes are intact, it is not easily available to substrates. LDH might be localized both in particulate and nonparticulate cellular material. It has been reported to be a mitochondrial enzyme
The mean β‐glucuronidase concentration in the adrenal homogenate of male patients with cancer was found to be significantly lower than that of male patients without cancer. The patient's age appeared to be without effect on the adrenal β‐glucuronidase concentration; an influence of the nutritional status independently of the disease could not be evaluated. Several cancer patients were treated with corticoids; this treatment was without effect on the adrenal β‐glucuronidase concentration. Histochemically, the highest β‐glucuronidase activity was localized in the zona glomerulosa in over 50% of cases; the other cortical layers or the medulla showed the highest activity in the remaining cases. The distribution of cell groups with β‐glucuronidase activity was patchy. The localization of β‐glucuronidase activity in the adrenals of patients with or without cancer was similar, but the number and intensity of areas with β‐glucuronidase activity was decreased in the adrenals from cancer patients. Although the actual function of β‐glucuronidase in the adrenal is not known, the preeminent localization in the glomerulosa and the lack of influence by stress and by steroid treatment on its concentration suggest a specific function in aldosterone metabolism. The changes in the adrenal β‐glucuronidase concentration in cancer patients may be an indication of disturbance in aldosterone metabolism.
The remote effects of cancer were studied by comparing the DNA, RNA, and histone concentrations in liver of patients with and without cancer. The cancers were either localized or disseminated, with or without liver metastases. In liver homogenates from patients with or without cancer, significant differences were not found in DNA and RNA concentrations. The nuclear RNA content was significantly increased in liver cells of cancer patients even when metastases were absent. In the metastatic tumor cells the DNA concentration was highly elevated. The nuclear RNA in damaged and regenerating liver cells was elevated similarly to that found with cancer patients. The increase of nuclear RNA, including probably messenger RNA, might be a nonspecific response to increased demand for protein synthesis or it might be highly specific for synthesis of cancer cell constituents.
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