Changes in nucleolar number of ascites tumor cells treated with actinomycin D.

In the nuclei of Ehrligh and NK/Ly mouse ascites tumor cells the number of nucleoli varies between 1 and 10. The average nucleolar number is 3.3 +/- 1.3 for both tumors. This value as well as the distribution of nuclei with various nucleolar number are parctically constant between the 5th and 15th day of transplantation. The nucleolar changes resulting from the effect of a single 200 mug/kg i.p. dose of actinomycin D take place in two phases, almost in the same manner for both tumors. Within 24 hours the mean nucleolar number decreases by about 20 percent accompanied by a diminution of size of nucleoli. 15 to 20 percent of nuclei does not contain real nucleoli but has small spots showing nucleolus-like staining ("scattered" nucleolar cells). The second phase is characterized by a 25-35 percent increase in the mean nucleolar number followed by a nucleolar enlargement. The process returns to normal within 6-7 days.

Hypoxanthine guanine phosphoribosyltransferase (HGPRT) activity in hybrids derived from HGPRT+ and HGPRT- mouse cells.

By utilizing the selection system, a population of hybrid cells with the gene coding HGPRT and sensitive to 8-azaguanine (8-AG) was isolated from a mixed population of hybrid cells derived from malignant diploid HGPRT+ mouse lymphosarcoma cells (LS/BL) and L cells resistant to 8-AG (HGPRT-, R-AG/20 strain). During back-selection of this hybrid population , cultivated in vitro, HGPRT- negative fractions of the cell population, resistant to 8-AG, appeared in a high frequency. As a rule, the telocentric chromosomes (or chromosome), originated from the HGPRT+ parental cells (LS/BL), were lost in these cells. The X chromosome of the LS/BL cells coding the HGPRT enzyme was not present in all cells of the hybrid HGPRT+ population. Hence it is assumed that the fusion of HGPRT+ (LS/BL) and HGPRT- (R-AG/20) cells resulted in a reexpression of the HGPRT activity from the R-AG/20 parental cells.

Heterogeneity of human adenocarcinomas of the colon and the stomach as regards sensitivity to cytostatic drugs.

In the present paper a test model was used to examine if human adenocarcinomas of the colon and the stomach are heterogenous as regards the sensitivity to cytosine arabinoside, melphalan, vinblastine sulphate, amethopterin and 5-fluorouracil in vitro. The effects of the five drugs were measured as the differences in incorporation of tritiated thymidine and deoxyuridine in drug-containing tubes and control tubes. It was found, that different parts of eleven colon and five stomach cancers differ significantly in their sensitivity to the same cytostatic treatment in vitro.

Occurrence of paraproteins in melanoblastoma.

Besides paraproteins in melanoblastoma, the study also follows the quantitative values of immunoglobulins during the course of the disease. According to the immunoglobulin values, the patients may be divided into two groups: those with a striking decline of IgG and a simultaneous generalization of the process; those without any significant alteration in the immunoglobulin values, but with paraproteins. The presence of the latter, particularly of gM became reflected in a stagnation of the entire process. Immunological results of sera from patients surviving 5 years, bear out this finding.

Atopy and cancer.

Malignancies were observed less frequently in the closest relatives of the patients suffering from hay fever with the most proved hereditary liability of atopy than in the relatives of control groups.

Vitiligo and malignant melanoma.

Six patients with vitiligo and malignant melanoma are reported. The relationship between vitiligo and melanoma seems to be a firm one. This process is supposed to represent an expression of induced autoimmunity.

Main principles of the organization of cancer control in USSR and selected data on cancer incidence.

The main principles and the structure of the cancer control organization in the USSR are described. The trends in the incidence of selected forms of malignant tumors and regional differences in USSR are documented with statistical data.

On the so-called MAC (Maximal Allowable Concentrations) for carcinogenic hydrocarbons.

The paper deals with some results of work done in the USSR to establish maximal allowable doses (MAC) for the carcinogenic hydrocarbon benza(a)pyrene in human environment. At the same time it is a brief review of some discussions on this item which took place in USSR and on the international level.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. II. Polarographic study of carcinogenic nitrogen compounds in dimethylformamide and comparison of half-wave potentials with quantum-chemical calculations of molecular orbitals.

Reduction of half-wave potentials and the mechanism of reduction of 20 polycyclic nitrogen compounds were studied on a dropping-mercury electrode in anhydrous dimethylformamide using tetrabuthylammonium perchlorate as the supporting electrolyte. The measured values of the reducing half-wave potentials of the polycyclic aza-compounds were compared in view of their carcinogenic activity with parental carcinogenic polycyclic hydrocarbons. Electrochemical measurements have confirmed that the size of the shift in reducing potentials towards the more positive values and the decline of the carcinogenic activity generally depend on the number and position of the nitrogen atoms in the molecule of the polycyclic nitrogen compound under study. At the same time, the experimental electrochemical measurements were matched with the results of the quantum-chemical calculations of the molecular orbitals and this showed a good agreement to exist between the values of reducing half-wave potentials obtained by experimental measurement and by calculation.

Incorporation of exogenous DNA and its localization in the chromosomes of the host cell.

Incorporation of isologous 3H-DNA of exogenous origin into chromosomes of the L cells was investigated by means of autoradiographical technique. It was shown that during short time intervals of incubation of 3H-DNA with the host cells (1--3 hr), nearly double quantity of the mitoses was labelled, when compared with 3H-TdR used as a control. During longer time intervals, no difference between number of the mitoses labelled with 3H-TdR and exogenous isologous 3H-DNA was observed.

Methotrexate and folic acid effect in normal and sarcoma 180 bearing mice.

Four- to six-fold surplus of folic acid in oral application reduced the toxicity of methotrexate administered repeatedly in high therapeutic doses. The therapeutic effect of methotrexate applied intraperitoneally to mice with the ascitic S 180 sarcoma, as measured by their survival, can be reliably demonstrated; moreover, the survival can be prolonged by adding folic acid into drinking water. In the solid form S 180 the intraperitoneal administration of methotrexate did not significantly reduce the weight of tumors of treated aminals as compared to untreated animals. The maximum tolerated dose of methotrexate was lower in animals with the ascitic tumor than in non-tumorous animals.

The influence of N-(2-hydroxyethyl)-palmitamide on virus-induced sarcomas in chickens and Rauscher leukemia in mice.

The effect of N-(2-hydroxyethyl)-palmitamide (PEA), an active endogenous compound, which may be useful in preventing virus infections of the respiratory tract, was studied in chicken sarcoma RBA-34 and mouse Rauscher leukemia. The experiments showed that PEA did not influence the induction, development and severity of experimental oncogenic diseases investigated.

Soluble melanoprotein of tumor origin.

The procedure for isolating soluble melanoprotein from human malignant melanoma was described. Electron microscopy confirmed the absence of any contaminating organized particles. The melanoprotein was brown hygroscopic substance with 8.8% of melanin, easily soluble in water. The solution revealed general absorption with a shoulder at 280 nm. Chemical composition was typical for a melanoprotein complex with characteristic high sulphur content (2.1%) and abundance in zinc (210 mug Zn/g dry sample). Sedimentation and electrophoretic properties indicated relative homogeneity. Similar substance could also be isolated from Harding-Passey mouse melanoma. Such soluble melanoproteins have been needed for their broad exploitation in tumor immunology.

Level of SH groups in paraproteinemic sera.

SH groups were determined in the sera of 131 subjects with paraproteinemia and in 100 healthy controls of a corresponding age. Significant decrease in the amount of SH groups in the serum was observed in IgG and IgM paraproteinemias.

Perspectives in scintigraphic detection of gynecologic tumors using labeled estrogen.

After having succeeded in imaging the prostate with 131I-Estracyt in our former experiments we tried to use the same method for scanning gynecological tumors. In about fifty per cent of the patients (34 cases) there was a convenient accumulation of the labeled estrogen, first of all the adenoid tumors, myomas of uteri and carcinomas can take up this radiopharmacon. Though the number of cases is rather low it is to be concluded that tumors of hormonal dependence can be scanned using estrogen hormon. Further investigations are in progress.

Serum immunoglobulin levels in cancer patients. I. Serum immunoglobulins and primary tumor localization.

A comparison was made between the mean values of immunoglobulin IgG, IgA and IgM in patients sera in various primary localizations of malignant tumors. The values ranged generally above the upper limit stated for the so-called healthy population, the highest being in Ca of kidneys of Grawitz type, Ca laryngis and Co bronchogenes. In the IgG class higher values appeared mainly in Grawitz tumor, however, a certain elevated level with respect to the other groups of malignancies occurred also in Ca vesicae urinariae and in Ca bronchogenes, but the differences are without statistical significance. No changes were observed in the IgM group.

A definition problem in cancer metastasis.

Orthodox definitions of cancer metastasis state that deposits which qualify for this name are those found distant from the primary tumor. This qualification has led to considerable confusion in the literature. A study of the etymology and pathology of metastasis leads to the conclusion that the essential feature is transportation and not distance. Accordingly, metastasis should be defined simply as "the formation of another growth in any site following the transportation of tumor cells from the initial growth". This definition will probably improve knowledge of the statistics of cancer metastasis.

Large-scale screening of the population of early detection of malignant tumors in the USSR.

Some selected data on cancer statistics in the USSR and results of the nationwide cancer screening activities are presented. The usefullness of some new methods in prophylactic examination is discussed.

Stimulation of rat liver regeneration by chloramphenicol.

The administration of chloramphenicol in high doses (300 mg per kg body weight in 6 hour intervals) to partially (70%) hepatectomized rats resulted in a marked stimulation of liver regeneration.

Replication of feline sarcoma virus in cat embryonic kidney cells in the absence of transformation.

The infection of cat embryonic kidney cells (CRC) with Gardner and Snyder-Theilen strains of feline sarcoma viruses (Ga-FeSV and ST-FeSV) do not lead to transformation and focus formation. The focus forming insusceptibility is shown to be stable and nontransmissable property of these cells. However, the CRC cells are permissive for ST-FeSV, and the viral production is 10 to 100 folds lower than in focus forming susceptible cat cells. Produced ST-FeSV(c) by CRC cells induced on cat embryonic cells FE in higher proportion round and fusiform (rf) foci and fusiform(f) foci. The f foci were not previously observed in original stock of ST-FeSV tested directly on FE cells. Attempts to detect some differences in morphology or in growth behavior between ST-FeSV infected and non-infected CRC cell population gave negative results.

The effect of long-term administration of N-(2-hydroxyethyl)palmitamide on the chemotherapy of RBA rat leukemia.

The effects of N-(2-hydroxyethyl) palmitamide (PEA) a natural and antitoxic substance on the treatment of RBA rat leukemia were studied. Repeated administration of PEA prolonged substantially survival of leukemic animals in the course of the treatment with cis-diamminedichlor-platinum (cis-Pt(II) in combination with cyclophosphamide, vincristine and methotrexate respectively. The most advantageous combination used was the cis-Pt(II) with methotrexate and PEA administration even improved the treatment results. The long-termed PEA treatment depressed first of all undesirable side effects and enabled to use higher therapeutic dosage of chemotherapeutics and improved the final results.

Further evidence on lymphocyte resistance of tumor-bearing in vitro rats to phytohemagglutinin.

A study was made of the survival of peripheral blood lymphocytes in short-term cultures with a standard dose of phytohemagglutinin (PHA) in rats during the course of methylcholanthrene (MC)-induced carcinogenesis. Peripheral blood lymphocytes of (BDXLW)F1 hybrid rats were tested at various time intervals following MC application. The investigation involved a group of rats in which tumors had not appeared as yet after MC application, a further group with developed tumors of varying sizes, and a third group in which the tumors were extirpated, their peripheral blood lymphocytes being examined both before and at a definite time interval after the extirpation. Finally, another group of animals was investigated in which no tumor appeared up to 14 months after MC administration. The higher survival values of lymphocytes in PHA cultures in animals with primary MC-induced tumors in comparison with those of the control animals were found to be related to the presence of a progressing tumor. The results are discussed in terms of a possible change of T and B lymphocyte ratio in the peripheral blood in the presence of a tumor antigen.

Variations in sensitivity of synchronized Chinese hamster cells to oxic and anoxic X-ray exposures.

V-79 Chinese hamster cells in monolayer cultures on glass surfaces were synchronized by treatment with hydroxyurea and exposed at different times thereafter to X-rays in the air or in oxygen-free argon. Survival determinations indicated that the oxygen enhancement ratio OER as expressed by the ratio of the respective D0 values varied over a narrow range in the different phases of the cell cycle. These changes resulted from cyclic alterations in both aerobic and anaerobic D0 values, and perhaps in n values.

The effect of anemia on the radiotherapy results of the uterine cervix cancer.

Relationship between hemoglobin level and survival and/or recurrence rate was studied in radiation treated group of postmenopausal women with uterine cervix carcinoma. The data suggest that anemia alters unfavorably the effectiveness of radiotherapy. A possible explanation of the lowered control rate is that due to deficiency of tissue oxygenation by reduced oxygen carriage proportion of hypoxic cells increases and impairs the radiosensitivity.

Long-term results in rectum carcinoma. Patients followed up during the period 1959-1968.

During the period 1959 to 1968, a total of 158 patients with carcinoma of the rectum were treated at the surgical department of the Oncological Institute in Bratislava. All these patients were retro spectively classified according to the TNM system into four clinical stages as follows: Stage I -- 26 (16.46%). Stage II -- 12 (7.59%), Stage III -- 61 (36.61%) and Stage IV -- 59 (53.39%) of the patient. Surgical treatment was supplemented with irradiation in 85 (53.73%) of the patients with chemotherapy in 15 (9.49%). All the findings were verified histologically. Favorable results as regards the 5-year survival rate in accordance with literature data were achieved in the early stages of the affection, while in advanced stages this survival rate was rather low, the majority of the patients died in the first and second year following initiation of treatment. The authors express the view that in future, oncologists will have to devote more attention to an early diagnosis and treatment of precanceroses, and this not solely in patients with a carcinoma of the rectum, but also in its other localizations.

Different inhibitory effect of nitrogen mustard (HN2) and TS-160 (HN3) on choline transport in L 5178Y lymphoblasts.

The inhibitory effect of the alkylating agents nitrogen mustard (HN2) and TS-160 (HN3) on the choline transport in L 5178Y lymphoblasts was studied. The two alkylating agents differed in the degree and in the nature of the inhibition of the process examined. Competitive inhibition of choline transport by HN2 was confirmed, whereas the noncompetitive inhibition by the less efficient inhibitor HN3 has been found. The results achieved indicate that in spite of the structural similarity between HN2 and HN3 only the former is transported into L 5178Y lymphoblasts by the choline transport carrier.

Light and electron microscopy of mouse lymphosarcoma LS/BL cells during the first hour after irradiation with x-rays.

Mouse lymphosarcoma LS/BL cells growing in tissue culture were irradiated with 100, 316 and 1000 R respectively and fixed 5, 15 or 60 minutes later. Semithin sections were studied under a light and ultrathin under an electron microscopes. Under the light microscope, differences between the morphology of individual nuclei were found in all groups, including controls; the rate of their occurrence was without any relation to the irradiation. They may reflect the differences in the state of LS/BL cells which were not completely adapted to cultivation in small glass tubes. On the other hand, the frequency of some ultrastructural changes seen under the electron microscope showed a relation to the irradiation. They were: undulation of the outer nuclear membrane and dilatation of the space between the outer and inner nuclear membranes, slots in karyosomes adjacent to the surface of the nuclei, enlargement of cisternae and vesicles of endoplasmic reticulum and Golgi apparatus. The importance of a careful examination of control groups in such experiments is stressed.

Kinetics of thymus-derived lymphocyte count changes in rats affected by graft-versus-host reaction.

The effect of GVHR on thymus-dependent lymphocytes of various lymphoid organs has been followed autoradiographically and by scintillation technique in a temporal dependence on the induction of the reaction. GVHR was induced in (BD X Lw) F1 hybrid rats with parental spleen (BD) cells. As marker of the thymus-dependent lymphocytes the in vitro 3H-uridine incorporation was used. Compared to B cells, T lymphocytes of rats have a higher ability of incorporating labeled uridine. T lymphocytes in peripheral blood and the thoracic duct achieved their peak at 3 or 4 days following GVHR induction. On the fourth day, simultaneously with a GVH-altered thymus a rapid decline in the number of these cells was also observed. A mobilization of T lymphocytes from the spleen and lymph nodes into the circulation already in the very first days of the reaction might be responsible for the peak seen in PBL and TDL. The GVH-alteration lasting 21 days caused an evident reduction of thymus-dependent lymphocytes in all the organs studied here. The immunological attack of GVHR is considered to be primarily responsible for the exhaustion of T cells. The discussion bears on the possibility of a more progressive action of GVHR on the more mature T lymphocyte subpopulation.

The comparison of aminotransferase activities in normal and Guerin epithelioma bearing rats.

The activities of 13 aminotransferawes in Guerin epithelioma and in the liver of normal and tumor bearing rats were investigated. Alanine and aspartate aminotransferases show the highest activity in all investigated tissues. In the liver of normal rats high arginine, tyrosine and phenylalanine aminotransferase activities were found. In tumor tissue high level of branched chain amino acid (leucine, valine and isoleucine) aminotransferases were observed. Increase in aminotransferase activities in the liver of tumor bearing rats was found. In order to elucidate the mechanism of this increase an inductive effect of hydrocortisone and protein free extract of tumor tissue on liver aminotransferases has been investigated. The tumor extract did not exert an inductive action. An inductive effect of hydrocortisone was not identical with the change in aminotransferase activities observed in the liver of tumor bearing rats.

Proteolytic activity in liver cells from mouse, rat, Ehrlich ascites carcinoma bearing mouse and in Ehrlich ascites carcinoma cells.

The activity of intracellular proteinases from Ehrlich ascites carcinoma bearing mice were compared with that from liver cells of normal mice and rats. The activity of intracellular proteinases was measured in the supernatant of Ehrlich ascites carcinoma cells homogenate. The activity of intracellular proteinases in normal mouse and normal rat liver were different at pH 3.5, pH 6.0 and pH 7.5. The activity in liver cells from Ehlrich ascites carcinoma bearing mouse at pH 3.5 was not significantly changed from normal mouse or rat liver cells, however at pH 6.0 and pH 7.5 the activity in the affected liver significantly decreased. The proteolytic activity in the supernatant of Ehrlich ascites tumor cell homogenate was 0.110 E750 mmu/mgN at pH 7.5, 0.154 E750 mmu/mgN at pH 3.5. The proteolytic activity at pH 6.0 was not detected in any experiment.