The effects of some carcinogenic nitroso compounds on the rat liver nucleolus.

The hepatocyte nucleoli of rats undergo a variety of specific and nonspecific alterations after the administration of 8 nitroso compounds and 5 corresponding non-nitroso compounds. After the oral administration of dimethylnitrosamine and diethylnitrosamine, and unusual segregation of the nucleolus was encountered in the cells with karyorrhexis. Most characteristic of the segregation are the scattered ribosome-like granules at the outermost layer of the altered nucleolus. Frequently microspherules with halos 150 nm in diameter are found in all rats treated with nitroso compounds, which have been reported to be carcinogenic in the organs other than the liver. With the exception of butylurea and butylamine no such specific microspherules were found in the nucleoli after the administration of corresponding non-nitroso compounds.     

The effects of some carcinogenic nitroso compounds on the rat liver nucleolus

Summary The hepatocyte nucleoli of rats undergo a variety of specific and nonspecific alterations after the administration of 8 nitroso compounds and 5 corresponding non-nitroso compounds. After the oral administration of dimethylnitrosamine and diethylnitrosamine, an unusual segregation of the nucleolus was encountered in the cells with karyorrhexis. Most characteristic of the segregation are the scattered ribosome-like granules at the outermost layer of the altered nucleolus. Frequently microspherules with halos 150 nm in diameter are found in all rats treated with nitroso compounds, which have been reported to be carcinogenic in the organs other than the liver. With the exception of butylurea and butylamine no such specific microspherules were found in the nucleoli after the administration of coresponding non-nitroso compounds.

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Über die Wirkung einiger cancerogener Nitroso-Verbindungen auf die Nukleolen von Leberzellen der Ratte

Zusammenfassung Die Nucleolen von Leberzellen der Ratte erleiden nach Gaben von 8 verschiedenen Nitrosoverbindungen und 5 entsprechenden Nicht-Nitrosoverbindungen eine Vielfalt von spezifischen und unspezifischen Veränderungen. Nach oraler Zufuhr von Dimethylnitrosamin und Diäthylnitrosamin wurde eine ungewöhnliche Segregation der Nukleolen in den Zellen mit Karyorrhexis beobachtet. Sehr kennzeichnend für diese Segregation sind verstreute Ribosomen-artige Granula in der äußersten Schicht der veränderten Nucleolen. Oft sind Mikrosphären mit Halos 150 nm in allen Ratten zu finden, die mit Nitrosoverbindungen behandelt wurden, welche als carcinogen für andere Organe als die Leber beschrieben wurden. Mit Ausnahme von Butylharnstoff und Butylamin wurden keine solche spezifischen Mikrosphären in den Nucleoli nach der Verabreichung der korrespondierenden Nicht-Nitrosoverbindungen beobachtet.

     

Inactivation of human tumor cell pro-urokinase by granulocyte elastase

Supernatant obtained from granulocytes stimulated in the presence of cytochalasin B by the chemotactic peptide N-formyl-norleucyl-leucyl-phenylalanyl-norleucyl-tyrosyl- lysine displayed an inhibitory effect on the plasmin-dependent conversion of tumor urokinase-type plasminogen activator proenzyme (pro-uPA) to the active form of uPA. Moreover, the supernatant was also found to inhibit the fibrinolytic activity of human vulva (A431) and breast (MCF7) carcinoma cell lines, which contain large amounts of pro-uPA, by 87% and 96%, respectively. By using eglin C (elastase inhibitor) and a monoclonal antibody to elastase (proteolytic activity blocker of the enzyme), elastase was identified as the key enzyme of the supernatant in these phenomena. Purified elastase converted pro-uPA to an enzymatically inactive molecule composed of two polypeptide chains of Mr = 33,000 and 22,000 linked to each other by a disulfide bond. Elastase-containing granulocytes were identified by immunohistochemistry techniques in the tissues of squamous cell carcinoma and adenocarcinoma of uterus. The cells were found close to the tumor cells and in the stroma surrounding the tumor nests. By immunohistochemical staining, uPA was also found in the tumor cells. Evidently, elastase released by chemotactically activated granulocytes, which are attracted into tumor tissues, may inhibit the conversion of pro-uPA to enzymatically active uPA in the tumor cells.