106 – Possible role of markers synthesized during cancer evolution: I- Markers in mammalian tissues

Authors : M. BELJANSKI, T. NAWROCKI, L. LE GOFF
IRCS Med. Sci. 14, 1986, pp. 809-810.

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ABSTRACT: Various trigger molecules (carcinogens, antimitotics, antibiotics, hormones, etc…) may induce mammalian cancer DNA chain relaxation correlated with an in vitro increase of DNA synthesis and the enhancement of cancer cell multiplication in vivo. In contrast, particular substances which contract cancer DNA chains inhibit cancer DNA synthesis and prevent cancer cell multiplication in vivo. During cancer evolution, large amounts of α-feto-protein (AFP), carcinoembryonic antigen (CEA) and calcitonin, may be synthesized. AFP normally produced by liver cells may accumulate in breast cancer tissues or in induced inflammatory lesions; it favours the accumulation of estrone in the new-born rat brain and affects the multiplication of estrogen-sensitive cells. The aim of the present work was to determine the effect of some embryonic antigens (markers) on normal and cancer DNA chain relaxation and DNA in vitro synthesis, in order to investigate their participation in the maintenance of the neoplastic state in vivo.

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102 – The in vitro Effects of Opines and Other Compounds on DNAs Originating from Bacteria and from Healthy and Tumorous Plant Tissues

Authors : L. LE GOFF, M. BELJANSKI
Expl. Cell. Biol., 53, 1985, pp. 335-350.

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ABSTRACT: Purified total DNAs were isolated from oncogenic or nononcogenic Agrobacterium tumefaciens cells as well as from normal and crown gall tissues. Opines (octopine, nopaline, lysopine), plant hormone (auxin IAA) and some carcinogenic compounds were used in order to correlate their effects on in vitro strand separation and synthesis of DNAs with in vivo tumorous cell multiplication. Octopine (or nopaline) induced chain opening of DNAs originating from octopine (or nopaline)-metabolizing bacteria and from same bacteria strain-induced tumorous cells. This phenomenon was measured by the increase in DNA hyperchromicity which is concentration dependent. The tested compounds stimulated the in vitro synthesis of the same DNAs. Under the same conditions, in vitro strand separation and synthesis of healthy plant DNA was not (or only slightly) enhanced, except in the case of particular hormone-connected healthy cell DNA. IAA and carcinogens stimulated in vitro synthesis and induced in vitro strand separation (dose-dependent effect) of DNAs isolated from crown gall cells and inducing bacteria. Compared to healthy cell DNAs, these DNAs were thus susceptible to structurally very diversified molecules and in this way behave as do mammalian tissue DNAs. The opine and IAA actions observed here were specific for plant tissue DNA; cancerous human or animal tissue DNAs were insensitive. By their presence in the crown gall cells, opines possibly maintain destabilized areas (required for rapid growth and division) on tumor cell DNA. The cooperative actions of IAA and opines as well as small RNA and RNA fragments on gene activation, might explain the autonomy of plant tumor cells..

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101 – Growth inhibition of crown-gall tissues in relation to the struture and activity of DNA

Authors : L. LE GOFF, J. ROUSSAUX, Y. AARON-DA-CUNHA, M. BELJANSKI
Physiol. Plant., 64, 1985, pp. 177-184.

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ABSTRACT: The growth of Crown-gall cells cultures in vitro (Nicotiana tabacum L. cv. White Burley and Parthenocissus tricuspidata cv. Veitchii) is inhibited by alstonine (BG-8), a plant alkaloid, the anti-cancer effect of which has previously been demonstrated on animals and plants. The growth of normal cells is only slightly affected. The inhibitory effect of BG-8 on crown-gall cells is antagonized byindole-3-ecatic acid (IAA) added to the culture medium. Kinetin associated with IAA does not prevent this inhibitory effect. BG-8 present in the culture medium containing the two types of hormones seems to modify the later hormonal requirement of Parthenocissus crown-gall tissues…

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100 – Three alkaloids as selective destroyers of the proliferative capacity of cancer cells

Authors : M. BELJANSKI, M. S. BELJANSKI
IRCS Med. Sci., 12, 1984, pp. 587-588

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ABSTRACT: Most of the anti-cancer drugs at present used in cancer chemotherapy exhibit tissue toxicity and cause severe damage to harmatopoietic cells. In addition, they are mutagenic and/or carcinogenic in animals and in plants. Using the Oncotest, we have selected three alkaloïds, alstonine, serpentine and sempervirine that possess the capacity to sistinguish in vitro between DNAs isolated from cancerous and healthy mammalian and plant tissues. They bind to the initiation sites of destabilized cancer DNA synthesis, without affecting that of DNAs from healthy tissues. Here we demonstrate that each of the three alkaloïds, which remain inactive against normal eukaryotic cells, selectively and completely destroys the proliferative potential of various established cancer cell lines maintained in and in vitro culture.

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99 – The Regulation of DNA Replication and Transcription. The Role of Trigger Molecules in Normal and Malignant Gene Expression

Authors : M. BELJANSKI
Experimental Biology and Medicine, vol.8, Karger (1983), pp. 1-190.

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ABSTRACT: This monograph explores basic processes of DNA replication and transcription in an effort to identify the mechanisms responsible for the release of genetic information and its role in the regulation of cellular events.

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97 – Tumor promoter (TPA), DNA chain opening and unscheduled DNA synthesis

Authors : L. LE GOFF, M. BELJANSKI
IRCS Med. Sci., 11, 1983, pp. 363-364.

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ABSTRACT: Tumor promoters accelerate the proliferative capacity of tumor cells although at high concentrations they may induce carcinogenesis in animals. Recently it was shown that TPA, (12-0)trtradecanoyl-phorbol-13-acetate), the tumor promoting phorbol ester, appears to act in a similar fashion on normal embryonal diploid and cancer cells. TPA induces differentiation of leukemic cells, activetes silent genes for specific r-RNA synthesis in hybrid cells and promotes cell proliferative capacity or phenotypic cellular changes. Here we report the in vitro effect of TPA on DNA secondary structure and DNA in vitro synthesis.

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93 – Agonist and/or antagonists effects of plant hormones and an anticancer alkaloid on plant DNA structure and activity

Authors : L. LE GOFF, M. BELJANSKI
IRCS Medical Science, 10, 1982, pp. 689-690.

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ABSTRACT: Using a biochemical assay system (Oncotest) we have shown that DNAs from cancerous mammalian and plant cells are destabilized compared to DNA from healthy cells. Cancer DNAs susceptible to the action of carcinogens or other different compounds exhibit in vitro and in vivo a high template activity in comparison to DNAs from healthy cells. We have also shown that alstonine, a plant alkaloïd prepared in our laboratory which selectively binds to DNA from cancer cells prevents DNA in vitro synthesis as well as cancer cells in vivo multiplication in animals and plants. It has slight effect on DNA from healthy cells. We describe here the effects of auxin (IAA) and kinetin (K) (two cell growth and division hormones in higher plant species) and that of alstonine (BG-8) on in vitro synthesis and strand separation of DNAs isolated from cancerous, habituated and healthy plant cells cultures in vitro.

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92 – Selective Inhibition of in vitro Synthesis of Cancer DNA by Alkaloids of ß-Carboline Class

Authors : M. BELJANSKI, M.S. BELJANSKI
Expl. Cell. Biol., 50, 1982, pp. 79-87

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ABSTRACT: The high template in vitro activity of native DNA from cancerous mammalian and plant tissues, compared to DNA from healthy tissues, enabled us to select substances which selectively inhibit cancer DNA synthesis. Among them, alstonine, serpentine, sempervirine and flavopereirine, all alkaloids which belong to the Beta-carboline class, distinguish cancer DNA from healthy tissue DNA inhibit DNA in vitro synthesis when native DNA from different cancerous tissues or cells is used as template. They have practically no effect on DNA from healthy tissues. The inhibitory effect of alkaloids is due to their capacity to form an ‘alkaloid-cancer DNA’ complex which has been characterized by use of the Sephadex column. Evidence is presented showing that these alkaloids inhibit the initiation of DNA synthesis but not chain elongation. The stimulating action caused by carcinogens during cancer DNA in vitro synthesis may be prevented and reversed by alkaloids. Furthermore, the stimulating action of steroids during in vitro synthesis of hormone target tissue DNA might be neutralized by alkaloids. However, at relatively high doses, steroids reversibly compete with alkaloids for binding sites on breast cancer DNA. This is not observed with DNA from nonhormone target tissues.

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