91 – Crown-gall Tumor Stimulation or Inhibition: Correlation with DNA Strand Separation

Authors : L. LE GOFF, M. BELJANSKI
Proc. Fifth Int. Conf. Plant Path. Bact. Cali, 1981, p. 295-307

Available in English only

ABSTRACT: The effects of the carcinogen dimethylbenz (a)anthracene, of antimitotic drugs (cyclophosphamide and daunorubicin), of the plant hormone (auxin IAA) and the antimitotic mitomycin C were investigated in vitro on cancer and healthy DNA from pea seedings, inoculated or not, with oncogenic agrobacterium tumefaciens. These substances stimulate in vitro both synthesis and strand separation of Crown-gall DNA as well as oncogenic A. tumefaciens DNA, while they have little effect on normal plant DNA as is the case with E.coli and non-oncogenic A. tumefaciens DNA. This correlates with the substance-enhancing-power on in vivo Crown-gall cell multiplication. Growth-stimulatory or inhibitory-effects are antagonized by the tumorless action of E. coli small size RNA-fragments. Plant ribonuclease is under control of all these compounds and the RNA-fragments compensate for increased or decreased ribonuclease activity induced by cyclophosphamide, daunorubicin, dimethylbenz(a) anthracene or auxin. There appears to be a correlation between ribonuclease activity and Crown-gall cell development.

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90 – Differential susceptibility of cancer and normal DNA templates allows the detection of carcinogens and anticancer drugs

Authors : M. BELJANSKI, L. LE GOFF, M.S. BELJANSKI
European Organization for Research on Treatment of Cancer
Third NCI-EORTC Sympmposium on new drugs in Cancer therapy, Institut Bordet, Bruxelles, 1981.

Available in English only

ABSTRACT: Based on the differential template activity exhibited by DNA isolated from cancerous and healthy human or animal tissues, the Oncotest is an accurate and rapid assay for the screening of carcinogenic compounds. Thus, in the presence of all necessary components for radioactive DNA synthesis by DNA polymerase, carcinogenic compounds, antimitotic drugs (and miscellaneous compounds), at given concentrations strongly stimulate the synthesis of DNA isolated from different cancer tissues, but only slightly enhance that of DNA from healthy tissues. Those carcinogens which cannot be characterized as mutagens in the Salmonella assay system, behave as carcinogens in the Oncotest. Carcinogenic potential of steroids can be shown by using the DNA from steroid hormone target tissue. There exists a common molecular mechanism through which carcinogens stimulate cancer DNA in vitro synthesis. Cancer DNAs are destabilized and in the presence of carcinogenic substances there is further DNA strand separation which accounts for the enhanced DNA synthesis. A correlation between in vitro cancer DNA synthesis, DNA strand separation and in vivo multiplication of cancerous cells can be demonstrated. Our assay system allows to detect those substances which selectively inhibit cancer DNA synthesis without affecting, in an appreciably way, that of DNA from healthy tissues.

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89 – Comparative study of Escherichia coli endotoxin, hydrocortisone and Beljanski leukocyte restorer activity in cyclophosphamide-treated rabbits

Authors : M. BELJANSKI, PLAWECKI
Proc. of the Soc. for Exp. Biol. and Med., 168, 1981, pp. 408-413

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ABSTRACT: The leukopoietic activity of Beljanski leukocyte restorer(s) (BLR(s)) (RNA-fragments obtained from Escherichia coli rRNA), E; coli endotoxin, and hydrocortisone administrated iv was compared in rabbits treated daily with high doses of cyclophosphamide (CP), a drug which decreases the circulating leukocyte count. Results showed that endotoxin and hydrocortisone responses, characterized essentially by granulocytosis occured at the 48th hour and remained, even during daily CP administration, within physiological limits for 3-5 days. No tolerance was induced with by administration of BLR in normal rabbits, even after 11iv injections, implying no depletion of bone marrow cells. In contrast, repeated endotoxin injections led to febrile and leukocytic tolerance. In addition, BLR induced normal leukocytosis and a biphasic fever response in endotoxin-tolerant animals. When BLR and endotoxin were mixed and administrated every day to rabbits, the animal became tolerant to endotoxin but gave a normal fever and leukocyte response to BLR, even after the 14th injection. The imbalance induced by CP administration in the granulocyte/lymphocyte ratio may be corrected following an injection of BLR. These data showed that the physiological activity of BLR in leukopoiesis was clearly distinguishable from that manifested by E. coli endotoxin and in the second instance by hydrocortisone.

NB : today, these extracts are named Realbuild

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88 – Correlation between in vitro DNA Synthesis, DNA Strand Separation and in vivo Multiplication of Cancer Cells

Authors : M. BELJANSKI, P. BOURGAREL, M.S. BELJANSKI
Expl. Cell. Biol., 49, 1981, pp. 220-231.

Available in English only

ABSTRACT: The chemicals 9, 10-dimethylbenzanthracene (DMBA), ethionine, daunorubicin, actinomycin D, 1-(2-chloroethyl-1)-nitrosourea (CCNU), steroids, croton oil and dimethyl-sulfoxide (DMSO) were used in order to correlate their effect on the in vitro synthesis of normal and cancer DNA, on DNA strand separation and on accelerated in vivo multiplication of cancer cells. All of the compounds tested strongly stimulate the synthesis of cancer DNA in vitro catalyzed by DNA-dependent DNA polymerase I and measured as an acid-precipitable labeled product. Under the same conditions, the synthesis of DNA originating from healthy tissues is only slightly enhanced, except in the case of croton oil and DMSO. These substances are almost equally active on cancer and normal DNA. Although both cancer and normal DNA contain a large amount of double-stranded regions, the extent of DNA strand separation measured by the increase in UV absorbance (hyperchromicity) in the presence of each compound tested is much higher for all cancer DNA than for corresponding normal DNA. In contrast, DMSO and croton oil do not appear to distinguish cancer DNA from normal DNA. Additive and differential effects of various compounds on cancer DNA strand separation can be observed. Small doses of DMBA and CCNU stimulate the multiplication of Ehrlich ascites tumor cells in vivo in mice. There is thus a possible correlation between DNA strand separation, DNA synthesis, multiplication and differentiation of cancer cells in the presence of the above compounds, which is different from the response of normal cells to these compounds.

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85 – Cancer/anti-cancer dual action drugs in crown-gall tumors

Authors : L. LE GOFF, M. BELJANSKI
IRCS Medical Science, 1979, 7, p. 475.

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ABSTRACT: Parallel studies on plant and animal tumor sytems provide insight into the basic cellular mechanisme of tumorogenesis. In the laboratory animals, drugs characterized as mutagens with the Salmonella assay system, as for example cyclophosphamide, may have an antimitotic effect and/or give rise to neoplasms. Various other in vitro carcinogen screening tests have shown that cyclophosphamide and daunorubicin have mutagenic and carcinogenic potencies. We give here a brief summary of the effect of two anticancer drugs, cyclophosphamide (Endoxan) and daunorubicin, on the heritable cellular change in pre-induced Crown-gall tumor development.

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84 – Oncotest: a DNA assay system for the screening of carcinogenic substances

Authors : M. BELJANSKI
IRCS Medical science, 1979, 7, pp. 476.

Available in English only

ABSTRACT: We describe a very rapid, sensitive and economic assay system (Oncotest) using purified DNA(s) from both cancerous and healthy human tissues (lung, breast, ovary and brain) and DNA dependent-DNA polymerase I, partly purified from Escherichia coli for detecting potential carcinogens. The amount of in vitro synthesized radioactive DNA as acid precipitable product is measured under strictly identical experimental conditions in the absence or presence of various concentrations of coumpounds to be screened. All known carcinogens and several drugs we tested strongly stimulate the syntheses of cancer DNA and only slightly that of DNA from healthy tissues. The results can be obtained within 1 to 4 hours.

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83 – Particular RNA Fragments as Promoters of Leukocyte and Platelet Formations in Rabbits

Authors : M. BELJANSKI, M. PLAWECKI
Exp. Cell Biol., 1979, 47, pp. 218-225

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ABSTRACT: Under well-defined conditions, ribosomal RNA from Escherichia coli is fragmented by pancreatic ribonuclease, leading to the appearance of particular RNA fragments. Some of these fragments act as primers for in vitro replication of DNA extracted from blood-cell and platelet-forming tissues. In experimental rabbits they restore in a rapid and harmless way normal circulating leukocyte and platelet levels when these have been drastically decreased by various chemotherapeutic agents mainly used in anticancer therapy. Imbalance between polynuclear and lymphocyte count provoked in rabbits by cyclophosphamide can be rapidly corrected by treating the animal with active RNA fragments.

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81 – Special short dual-action RNA fragments can both induce and inhibit crown-gall tumors

Authors : M. BELJANSKI, L. LE GOFF, Y. AARON-DA-CUNHA
Proc. 4th Conf. Plant Path. Bacteria, Angers, 1978, pp. 207-220.

Available in English only

ABSTRACT: When ribosomal RNA which contains an excess of purine nucleotides is subjected to mild degradation by a specific ribonuclease, we can isolate specific RNA-fragments which, in vitro, can be described into complementary DNA by an RNA dependent DNA polymerase partially purified from Escherichia coli extracts. These RNA-fragments can either stimulate or inhibit development of crown-gall tumors induced by inoculation of Agrobacterium tumefaciens (oncogenic strain B6) into decapitated germinating pea seedlings (Pisum sativum L cv. Annonay). Stimulation or inhibition of tumor development depends on the time at which the RNA-fragments have been introduced into the bacteria-infected wound. Interaction between RNA-fragments and auxin was also studied. Results obtained both in vitro and in vivo will be described.

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79 – Nouvelles substances (R.L.B.) actives dans la leucopoïese et la formation des plaquettes

Authors : M. BELJANSKI, M. PLAWECKI, P. BOURGAREL, M. S. BELJANSKI
Bull. Acad. Nat. Med., 1978, 162, Volume n°6, pp. 475-781.

Available in French only, Abstract in French and English.

ABSTRACT IN FRENCH : Lorsque les taux de leucocytes et de plaquettes dans le sang ont été abaissées par l’effet secondaire de certaines chimiothérapies, ces taux peuvent être ramenés rapidement et sans danger à leurs valeurs normales par les ARN-fragments, les R.L.B.

ABSTRACT IN ENGLISH : When the leucocytes and blood platelets have their counts reduced in the blood following chemotherapy, they can be rapidly and safely, restored to normal values by injecting cellular ARN fragments, which the authors call R.L.B. factors.

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78 – Découpage des ARN ribosomiques d’Escherichia coli par la ribonucléase U2 et transcription in vitro des “ARN-fragments” en ADN complémentaire

Authors : M. BELJANSKI, P. BOURGAREL, M.S. BELJANSKI
C.R. Acad. Sci., 1978, 286, pp. 1825-1828 (série D).

Available in French only

ABSTRACT: Under well defined conditions ribosomal RNAs purified from Escherichia coli can be degraded by ribonuclease U2 giving rise to RNA fragments of 60-70 nucleotides. In vitro, these fragments are efficently transcribed into a complementary DNA by DNA polymerase RNA dependent, partially purified from extracts of E. coli. In vivo, “RNA-fragments-U2” inhibit the development of plant tumors.

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