Zeitschrift fur Krebsforschung und klinische Onkologie. Cancer research and clinical oncology最新文献

An increase in the number of examples of emperiopolesis, i.e., cells within cells, was observed subsequently to addition of Bt2cAMP to spinner flask cultures of JB-1-E tumor cells. A conspicuous arrangement of microtubules and 100 angstrom filaments in the tumor cells involved in emperiopelesis was observed. Absence of emperipolesis in cultures treated with cytochalasin B indecates a possible role of the contractile microfilaments in the events leading to emperiopolesis. The significance of and the term emperipolesis are discussed.

Eight patients suffering from wide-spread malignancies presented with a severe microangiopathic haemolytic anaemia (MHA) without gross evidence for coagulation abnormalities. The common feature in these patients was bone marrow infiltration with malignant cells, suggesting a pathogenic link between bone marrow carcinosis and red cell destruction. Furthermore, it is concluded that MHA is a rare complication of malignancy and a terminal syndrome rather than an early manifestation of the disease.

Ether-permeabilized (nucleotide-permeable) Escherichia coli cells exhibited DNA excision repair when exposed to the following carcinogenic K-region epoxides: 7-methyl- and 7,12-dimethyl-benz[a]anthracene-5,6-oxide, chrysene-5,6-oxide and benzo[a]pyrene-4,5-oxide. This DNA excision repair was missing in uvr A and uvr B mutant cells. The K-region epoxide phenanthrene-9,10-oxide was ineffective in all E. coli strains tested. In contrast to the K-region epoxides which where found active only in wild type cells, 1,2,3,4-diepoxybutane and the 6,7-epoxides of the tumor promoter TPA (12-O-tetradecanoyl-phorbol-13-acetate) elicited DNA repair in uvrA, uvrB mutant cells as well. Enzymic activities catalyzing particular repair steps were identified by determining a) repair polymerization and b) size reduction of denatured DNA. A) An easily quantifiable effect in E. coli wild type cells was epoxide-induced repair polymerization. None of the K-region epoxides tested stimulated DNA repair synthesis in uvrA, uvrB mutant cells, indicating that the uvrA-, uvrB-controlled UV-endonuclease initiated excision repair by cleaving epoxide-damaged DNA. 1,2,3,4-Diepoxybutane and the TPA-6,7-oxides induced DNA repair polymerization in uvr-deficient cells, although to a lesser extent than in wild type cells, suggesting the involvement of uvr-independent incision steps. None of the epoxides induced repair polymerization in a mutant (polA107) lacking the 5'--3'exonucleolytic activity of DNA polymerase I (exonuclease VI). The absence of any repair polymerization in the polA107 mutant indicates that the exonuclease VI plays a central role in removing epoxide-damaged nucleotides. As evidenced by greatly reduced levels of repair polymerization measured in polA1 cells, DNA polymerase I was the main polymerizing enzyme. b) As a consequence of treatment with 7-methyl-benz[a]anthracene-5,6-oxide, DNA from wild type cells, contrary to uvrA mutant cells, showed size reduction after denaturation and sedimentation in alkaline sucrose gradients. This is explained by repair-specific endonucleolytic cleavage of damaged DNA. The incision required the presence of ATP indicating that functional UV-endonuclease needs ATP as a cofactor.

Mice have been immunosuppressed with cyclophosphamide, cortisone-acetate, irradiation, or Ehrlich ascitic fluid (EAF) and then grafted with Ehrlich tumor or with one of the following strain-specific tumors: thymoma, methylcholanthrene-induced fibrosarcoma, B-16 melanoma, lymphatic leukaemia, and myeloid leukaemia. Immunosuppression of the host influenced very differently the growth of transplanted malignancies. The growth of thymoma and of Ehrlich tumor was regularly enhanced. The growth of fibrosarcoma and of melanoma, on the other hand, was retarded in mice pretreated with EAF and X-rays, or remained unchanged in mice pretreated with drugs. Leukaemia growth was not influenced by any immunosuppressive treatment; the only exception was enhanced growth of lymphoid leukaemia in animals pretreated with EAF. Thus different tumors grew differently in animals immunosuppressed by the same immunosuppressive agent, while different immunosuppressive treatment changed the growth of one particular tumor always in the same way. From this we concluded: (1) there is no rule as to how immunosuppression of the host will influence tumor growth; and (2) the way in which the malignant growth will be changed depends mainly upon the type of the tumor and probably not very much upon the type of immunosuppressive treatment.

Chile being the only country in the world producing natural fertilizers (NaNO3 and KNO3), it uses very large quantities of them for agricultural purposes. Since in early 1970 Zaldívar first related the use of fertilizers to stomach cancer mortality, it is of key interest to know the amount of nitrogen fertilizers used, expressed in tons of N, by province, for the period from 1945 to 69. Of a total of 420,750 tons of N for the nation, 238,950 tons were used in the high-risk provinces for stomach cancer (Colchagua, Curicó, Talca, Maule, Linares, Nuble, Concepción, Bio-Bio, Arauco, Malleco, Cautín). On the other hand, in the low-risk provinces (Tarapacá, Antofagasta, Atacama, Magallanes) only 2,550 tons were used. In Chile, the use of fertilizers increased from 37,550 (1945-50) to 185,050 (1965-69) tons of N.

4-Chloronitrosopiperidine was administered to a group of 15 male Sprague-Dawley rats as a 0.005% solution in drinking water for 27 weeks. Of the 15 animals, 12 died with tumors induced by the treatment, half of them by the 41 st week; all 15 were dead at 58 weeks. Seven rats had liver tumors, 5 had esophageal tumors, 2 had tumors of the nonglandular stomach and 2 had tumors of the nasal turbinates. Several rats had tumors of more than one organ.

A simple mathematical function is established which renders the increase of the labelling index during continuous labelling of an exponentially growing tumor. By known values of proliferative fraction, mean cell cycle time and tumor doubling time, the mode and extent of cell loss is determined. Three models for different modes of cell loss are introduced: Model A for cell loss equally affecting proliferative and resting cells; Model B for cell loss predominantly affecting one of the two cell compartments; Model C for cell loss during mitosis. The range of validity of the model function is specified. Experimental data of a Polyoma virus-induced renal sarcoma of the rat provide an example of applicability of the theoretical model.

Ether-permeabilized (nucleotide-permeable) Escherichia coli cells respond to alkylating and arylalkylating carcinogens with DNA excision repair, as assessed by their stimulation of DNA repair synthesis. In the present work, we have investigated whether DNA repair synthesis in ether-treated E. coli cells can serve as a general indicator to monitor the DNA-binding of carcinogens, mutagens and antitumor agents. Therefore, a standard assay was developed and comparative analyses were performed on 11 ultimate carcinogens, 10 proximate carcinogens, 2 tumor promoters, 6 mutagens, and 12 antitumor agents. All ultimate carcinogens (alkylating, acylating, arylalkylating agents) and mutagens (e.g., hydrogeen peroxide, acridine derivatives) caused DNA excision repair in wild type cells as measured by [3H] dTMP incorporation and simultaneously inhibited replicative DNA synthesis to various extents. Control experiments with the mutant cells uvrA and uvrB were performed to determine whether the pyrimidine-dimer-specific UV-endonuclease was involved in the removal of DNA damage. This was found to be true for the ultimate carcinogens (Ac)2 ONFln, mitomycin C, and for very reactive alkylating carcinogens. None of the ultimate carcinogens induced repair polymerization in mutant cells lacking the 5'-3' exonucleolytic activity of DNA polymerase I. Proximate carcinogens, such as Me2NNO, 4-nitroquinoline-1-oxide and aflatoxins, did not induce excision repair in the standard assay, probably because of the inability of E. coli to perform the activation steps necessary for covalent DNA-binding. However, Me2NNO, when pretreated with Udenfriend's hydroxylating mixture, gave rise to a low level of repair polymerization in ether-treated cells. Intercalating mutagens, such as quinacrine and ethidum bromide, inhibited replicative DNA synthesis. However, they were not found to be repair-inducers. THE TUMOR PROMOters TPA and phorbol-12,13-didecanoate did not cause excision repair, even when applied at high concentrations, nor did they inhibit repair synthesis stimulated by MeNOUr or (Ac)2 ONFln. The antitumor agents may be classified into two groups on the basis of the influence they exert on DNA synthesis: members of the first group (involving BCNU and bleomycin) stimulate repair polymerization and, in addition, inhibit DNA replication. These compounds are known to bind covalently to DNA. The second group of drugs (including adriamycin and cis-Pt(II)diammine complexes) inhibits DNA replication without stimulating repair synthesis. The predominant DNA-interaction of these compounds is known to be a non-covalent (i.e., intercalative, electrostatic) binding. Our experiments show that the ether-permeabilized E. coli cell can be successfully used to test ultimate carcinogens, mutagens and antitumor agents for repair-inducing and replication-inhibiting activity. The standard test might be extended to pre- and proximate carcinogens, provided these can be suitably activated.