The effect of repeated dose of x-irradiation on the progress of HeLa cells through the cell cycle.

In contradistinction to the increased fraction of HeLa S 3 cells in S phase after irradiation by a single dose in a range of 25--200 R, cultures irradiated by a second dose at time of morphologic restitution of mitotic activity exhibited decreased fraction of cells in S phase. The interpretation is that passage from G1 to S was reduced due to disturbances in subsystems which have not been fully repaired.

Deoxypyrimidineuria in the course of chemotherapy in M. Hodgkin.

In patients with Hodgkin's disease the excretion of pyrimidine deoxyribonucleosides in urine was followed up within the course of 92 chemotherapeutical series with cytostatics of COOP group. In 14-day chemotherapy series, the excretion of deoxycytidine, deoxyuridine, thymidine, and their sum was significantly increased. In this paper the results are analyzed and a possibility of utilization of this finding for the judgment in the clinical course of the disease is considered.

Trends in morbidity on the basis of newly-reported cases of malignant skin melanoma (172 ICD) and other skin neoplasms (173 ICD) in Czechoslovakia during the period 1961--1972.

According to newly-reported cases of all malignant neoplasms of the skin (172 + 173 ICD) morbidity rate for the period 1961--1972 showed a rising trend of statistical significance only in Bohemia; while in Slovakia it persisted at a practically steady level throughout the period followed. Malignant skin melanomas (172 ICD) were on the increase in both regions, the rate being of statistical significance only in men in Bohemia. Morbidity from other malignant skin neoplasms (173 ICD) during the same period showed a stable pattern in Slovakia while it rose steadily in a significant degree in both, males and females in Bohemia. The causes for these varying trends must be further analyzed.

Trends in mortality rate from malignant skin melanoma and other malignant skin neoplasms in Czechoslovakia during the period 1921--1970.

Mortality from malignant skin melanoma (172 ICD) has an ascending trend in Czechoslovakia (CSSR) the rate being higher after the year 1960 in Bohemia (CSR) than the Slovakia (SSR). Mortality from other malignant neoplasms of the skin (173 ICD) declines; this decline for the whole of Czechoslovakia has been statistically influenced mainly by the lower death rate from this cause in Bohemia, for in Slovakia this mortality rate has risen, although significantly only in women. The proportion of deaths from malignant skin melanoma (172 ICD) out of the total number of deaths from malignant skin neoplasms (172 + + 173 ICD) is relatively low in Czechoslovakia--lower in Slovakia than in Bohemia.

Inverse diurnal variation of blood plasma 11-hydroxycorticosteroids level in cancer patients.

The plasma level of 11-hydroxycorticosteroids was examined twice a day by means of MATTINGLY'S fluorometric method in patients with malignant and other chronic diseases and in control subjects. Higher values in the afternoon or the same as those in the morning were found in each case of malignant disease. This change of physiological diurnal rhythm was not observed in the vast majority of healthy subjects or in patients with non-cancerous diseases.

The reaction of Cytembena with cellular thiol compounds.

Cytembena has been shown to undergo a rapid addition reaction with a number of thiol compounds, including glutathione and cysteine, resulting in alkylation of the sulphur. Administration of Cytembena to Yoshida sarcoma cells and to L1210 leukemia cells resulted in a loss of titratable thiol groups within the cells, though the loss of thiol groups caused by pharmacologically active doses of the drug was not sufficient to account, in itself, for the observed toxicity. The addition product of Cytembena and glutathione was isolated and tested for cytotoxicity; it was much less effective than free Cytembena. It is concluded that this reaction acts as a route of detoxification of Cytembena.

Leukemia of BALB/c mice induced by cellfree filtrate from transplantable Thurzo--Svec rat leukemia.

Leukemia was produced in adult BALB/c mice inoculated with cellfree filtrate derived from cells of transplantable Thurzo-Svec rat leukemia. The leukemogenic activity of 20% filtrates was 10(8) ID 50 per ml. Leukemia induced in mice with rat materials was serially transplantable by cellfree filtrates of leukemic tissues and plasma to the same strain of mice.

E rosettes in lymphoproliferative diseases.

Results are given of investigations of E rosettes in patients with chronic lymphadenosis and malignant lymphoma. The quantity of E rosettes was expressed both as per cents and in absolute numbers calculated from the total amount of lymphocytes in peripheral blood. In the normal controls the percentage of E rosettes was 58% on average while in patients with chronic lymphadenosis it was found to have decreased significantly down to a mean of 6%. However, in absolute values the number of rosette forming lymphocytes was normal and even higher. In the group with malignant lymphoma the percentage decrease was less striking than in those with chronic lymphadenosis, however, the absolute number of rosette forming lymphocytes was always found to be lowered because of evident to considerable lymphopenia. A dynamic study of the observed changes might contribute to a knowledge of the pathophysiology of lymphoproliferative diseases.

Complement consumption in fresh blood sera by double culture of Paramecium caudatum and Aerobacter cloacae compared with survival and stage of disease in some malignant tumors in man.

Using the complement consumption test by double culture of Paramecium caudatum and Aerobacter cloacae (DPA) as antigen we examined blood sera and compared survival rates and stage of disease in 124 patients with carcinoma of cervix uteri, corpus uteri, ovaries and breast. The evidence suggests that bacteria Aerobacter cloacae constitute the proper antigenically effective substances of DPA. The intensity of reaction and therapy the relative titres of antibodies detected by the test were expressed by the amount of complement consumed in the reaction and designated by the abbreviation "NMHD", i. e. number of minimum haemolytic doses of complement fixed by antigen in the reaction. Patients with NMHD above 8 (i. e. with an intensive reaction corresponding to a high level of antibodies) exhibited partly higher three-year survival rates -- starting from the time of diagnosis, partly more often the clinical stages of disease I or II as compared with patients with NMHD below 4. The best survival rates were found in patients with NMHD above 8 and clinical stage I or II. NMHD values in patients with the initial period of disease and in healthy women did not differ substantially.

Changes in human lymphocyte subpopulation in Hodgkin's lymphoma.

An investigation of 33 patients with Hodgkin's lymphoma--both treated and untreated--has revealed lymphocytopenia and a significant decline in the absolute number of T lymphocytes labeled with rosettes with sheep erythrocytes to be due in these patients not to the tumorous disease itself, but probably to the intensive nature of the therapy. A marked decline in the absolute number of B lymphocyte subpopulation, determined by the formation of rosettes with mouse erythrocytes, occurs during a fresh relapse of patients with an active Hodgkin's lymphoma. This decline is probably independent of the preceding treatment, of the clinical stage of the disease and of its histological type.

T and B lymphocytes in malignant melanoma patients.

The method of formation of spontaneous (E) and immune (EAC) rosettes and the test of lymphocyte survival in short-term cultures with phytohemagglutinin (PHA) have been used as parameters of cellular immunocompetence in 64 patients with malignant melanoma and 33 control donors. Significant changes have been found in the number of T lymphocytes whose values corresponded to the clinical stage as well as to the clinical postoperational course in the patients. A decreased number of T lymphocytes was a sign of progression of the disease, while a normal value indicated remission. Lowered ratios of T lymphocytes were followed by an increased proportion of both the B lymphocytes and the null, nonrosetting cell elements. The results in patients with malignant melanoma permit the relevant parameters to be considered as an effective in vitro correlate of cellular immunity of these patients.

Ultrastructure of human uveal melanomas cultivated in vitro.

Ultrastructural characteristics of four mixed-cell type human uveal melanomas cultivated in vitro were described. The authors stress the significance of melanosome microtubules in the process of melaninisation. They also stress the significance of smooth membraness for the formation of premelanosomes. The question of differentiation between melanocytes and lysosomes in ultrastructure is discussed.

Cytology of delayed hypersensitivity reaction in patients with malignant tumors.

A modification of the "skin window" method is proposed for investigation of delayed hypersensitivity in patients with tumors. The principle of the modified method consists in an antigen injection into the site of lesion. Patients with tumors showed a strikingly lowered lymphoid cells and eosinophilic and basophilic granulocytes than the controls.

Are the tumor cells of the G2 period of the cell cycle sensitive to the immune pressure?

The present work was aimed at analysing as to whether the cell loss is random within the cell cycle or not. In order to verify the former statement two regressing tumor systems: Ehrlich ascites carcinoma transplated into rats (heterologous graft) and BN/b lymphoma implanted into immunized BN/b mice (syngeneic graft), were used. Both tumor lines were examined by means of double labeling method coupled with short colcemide block. In the case of regressing tumors the cell flux into DNA synthesis was found to be at the same level as for the growing tumors. On the contrary, the flux into mitosis was much lower for regressing tumors than for growing ones. The above results suggest the immune attack on tumor cells while in the G2 phase of the cell cycle.

The effect of dibromodulcitol (Elobromolr, Mitolactolr, nsc 104 800) on the postoperative recurrences of the Guerin carcinoma of the rat.

In all cases of Guerin carcinoma of the rat the recurrence of the tumor in 7-10 days can be observed following surgical removal. Local treatment with Dibromodulcitol combined with intraperitoneal administration of the same drug results in delayed occurrence of tumor recurrences, the growth of which is slower, and in a significant increase of life span of the animals. In exceptional cases no recurrence appeared. The local treatment combined with intraperitoneal administration was the most effective. Peroral treatment was also effective although in a lesser degree.

Incorporation of 3H-dibromodulcitol and 3H-dianhydrodulcitol into ascites tumor cells. Autoradiographic study.

The incorporation of 3H-Dibromodulcitol and 3H-Dianhydrodulcitol into S37 ascites tumor cells has been studied with autoradiography. Both drugs war incorporated very rapidly into the cells. The labeling of nucleus was higher than that of cytoplasm. A slight accumulation of grains was found above the condensed chromatin and along the membranes. The uptake of DAD has been more intensive than that of DBD.

Structural and metabolic characterization of RNAs from rats with experimental Guerin tumor - I. Nucleotide composition of RNAs from the liver and tumor tissues of rats.

The characteristics of the ribonucleic acids of Guerin tumor was the subject of this work. The effect of tumor development on the structure of the ribonucleic acids in the liver of tumor bearing rats was studied. Some differences of nucleotide compositions in RNAs isolated from subcellular fractions of liver of control and tumor bearing rats and of cancer tissue were observed. The nucleotide compositions of cancer nuclear RNA is distinctly different from liver RNA. The changes in primary structure of liver RNAs due by development of tumor in rats may be result of metabolic peculiarities of these RNAs.

Structural and metabolic characterization of RNAs from rats with experimental Guerin tumor - II. metabolic peculiarities of RNAs from the liver and tumor tissues of rats.

Metabolic peculiarities of RNAs in the liver of the tumor bearing and in the tumor tissue were found. The synthesis of nuclear RNA in liver of tumor bearing rats is distinctly disordered in comparison to that of control rats. The level of 14C-orotic acid incorporation into RNA of cancer tissue is manifold lower than that into the liver RNA. The studies on turnover rate showed the metabolic heterogeneity of the nuclear RNAs. The part of them showed a short turnover, the other RNAs were degraded much slower.

Serum immunoglobulin levels in cancer patients. II. Serum immunoglobulins and stage of tumor progress.

A study of the IgG, IgA and IgM levels in relation with the clinical course of the tumor disorders revealed the IgG values to correlate with the progress of the disease. Their levels were found to rise from stage I to stage III of the classification according to tumor progress, the difference between these stages being of statistical significance. A similar trend, though statistically nonsignificant, was noted also in IgA levels, but these proved right from the start to be higher than the values reported for the apparent normal population. The rising tendency in the IgG--and the less striking one in the IgA levels were also confirmed by a comparison of the mean values of collections separated by a definite time interval in the same patients and this both for the deteriorated and unchanged cases, but not for the group of improved patients.

Effect of passages of Morris hepatoma 5123D in F1 (Buffalo X Wistar) rats on permanent decrease of gamma-glutamyltranspeptidase activity.

The Morris hepatoma 5123D after at least two passages in F1 (Buffalo X Wistar) rats shows quicker growth than the original tumor and bearers of it have much lower gamma-glutamyltranspeptidase activity in serum, urine, tumor and in some other organs. This new variant of the hepatoma was labeled as hepatoma 5123D/AS. Simultaneous implantation of hepatomas 5123D/AS and 5123D in the same rats prevents the increase of serum gamma-glutamyltranspeptidase activity. After surgical removal of the former tumor, the enzyme activity in serum quickly increases. No significant differences in some other peptidase activities were observed between the variant and hepatoma 5123D.

The influence of pH on the excision of UV-photoproducts from HeLa cells.

Excision of pyrimidine dimers with pH decreasing in UV irradiated HeLa cells can be depressed. This depression is independent of the UV dose within the investigated range. The excision capacity of HeLa repair system from absolute amount of excised dimers is shown.

Virological and immunological characteristics of tumors induced in adult rats by Rous sarcoma.

Forty primary tumors of Wistar rats and first seven passages of tumors of August rats were investigated by different virological and immunological methods. The tumors were induced in adult rats by Schmidt--Ruppin strain of Rous sarcoma. Based on the virus-cell interaction, the tumors were divided into four groups. The first group of tumors of Wistar rats (2 out of 40) contained mature RSV and viral antigens could be detected by means of the FA test, while the rats had virus neutralizing antibodies in their sera. The second group of Wistar rat tumors (19 out of 40) and August rats tumors contained virus connected with the cells. The third group was composed of "virus-free" tumors of Wistar rats (8 out of 40). Application of the method of cells association increased rescue RSV in tumors of the 2nd group by 2--4 fold and caused activation of the virus in tumors of the 3rd group. Irradiation of rat tumor cells with a dose of 5000-10 000 R did not enhance the rescue or activation of oncogenic virus in any case. In tumors of the second and third group viral antigen was detected by the FA test in 47% and gs antigen by the CF test in 17%. gs antibodies were found in 29% of the sera from rats with these tumors. The 4th group of Wistar rats tumors were "virus-free" (11 out of 40) showing a negative effect of RSV activation. These tumors with one exception contained no virus antigen, and there were no antibodies against them in sera of the rats.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. IV. Polarographic study of carcinogenic and noncarcinogenic hydrocarbons in ethylenglycolmonomethylether.

An experiment was carried out to determine whether there is any correlation between the values of polarographic reduction potentials of polycyclic hydrocarbons and their carcinogenic activity. A comparison of half-wave potentials of polarographic wave I and II of pyrene benzologs revealed that the carcinogenic ones become reduced in ethylenglycolmonomethylether on a mercury dropping electrode at more positive potentials than the inactive benzo- and dibenzopyrenes. The discussion bears both on the reduction mechanism of the compounds and on the relationship between the half-wave potentials and the absorption electron spectra measured in the same solvent.

Study of tumor specific immunity in rats using in vitro migration inhibitory tests.

Serum enzyme activity in bone tumors and osteomyelitis (LDH, GOT, GPT, CPK, CHE, ALP, AP, PP, ALD).

Enzyme activity of lactate dehydrogenase, glutamate-oxalacetate and glutamate-pyruvate transaminase, creatine phosphokinase, cholinesterase, alkaline, acid and prostatic phosphatase and aldolase has been studied in a total of 213 subjects, of whom 97 were of good health, 63 had bone tumors and 53 suffered from osteomyelitis. The activities of the majority of the enzymes were found to become significantly changed in comparison with the norm. In both patient groups, the more striking differences being noted in that of osteomyelitis. However, enzymatic activity alone does not allow to differentiate the group of bone tumors from that of osteomyelitis, the differences between these two groups not being of significance in any one of the enzymes followed.

Body temperature and tumor virus infection. I. Tumorogenicity of Rous sarcoma virus for reptiles.

Rous sarcoma virus (RSV) was oncogenic for the following nine species of reptiles representing 6 families from Chelonia and Squamata orders: family of Testudinidae: 1. Testudo horsfieldi, family Agamidae: 2. Agama sanguinolenta; 3. Agama erythrogastra, family Lacertidae: 4. Eremias persica; 5. Eremias velox; 6. Eremias grammica, family Scincidae: 7. Eumeces taeniolatus, family Boidea: 8. Erix tataricus, 9. Ancistrodom blomhoffi. RSV did not induce tumors in 13 studied species of reptiles. Histologically 26 reptile tumors studied were polymorphous sarcomas with spindle-shaped (fibroblast-like), round and polygonal macrophage-like cells and sometimes peculiar giant polynuclear cells. Chromosomal analysis showed that reptile tumors arose out of reptile cells. RSV was pathogenic for adult reptiles. Reptile tumors did not contain a mature infectious virus. The tumors of 2 snakes were virogenic. The effect of increased temperature at the body level on the transformation of a symptomless viral infection into a viral disease is discussed in the evolutionary aspect.

Effect of heterologous antimacrophage serum on growth of Rous virus-induced sarcoma in the allogeneic and syngeneic system.

The effect of heterologous antimacrophage serum (AMS) and normal rabbit serum (NRS) on the immune reaction against Rous virus-induced sarcoma (RSL) was studied in rats. The growth of RSL sarcoma transplanted against the H-1 barrier in AMS-treated rats was more progressive than in the untreated or NRS-treated control group. On the other hand, the growth of RSL sarcoma was significantly suppressed in syngeneic AMS- or NRS-treated recipients compared to the untreated control rats.

The cell-growth inhibitory effect of interferon. Studies of a resistant cell-subline.

Studies performed in the CSV subline of mouse L-cells suggest that activated endogenous and/or exogenous viral infection might be the factor that modifies the cell surface and, in consequence, the sensitivity of the cell to the cell-growth inhibitory action of interferon. In contrast with the parental L-cells, the CSV subline obtained by prolonged passage of L-cells in the presence of interferon shows an altered electron microscopic morphology, absence of C type particles and a decreased agglutinability with Concanavalin A. It is resistant to the cell-growth inhibitory effect of interferon but retains the sensitivity toward its antiviral effect. However, the sensitivity of the CSV subline toward the cell-growth inhibitory effect of interferon increased significantly after treatment with 5-iododexyuridine, infection with the Harvey strain of mouse sarcoma virus and/or prolonged passages in vitro. In this respect, the CSV subline resembles the primary mouse embryonic cells. Since sensitivity of CSV cells increased also after treatment with cyclic 3'-5' adenosine monophosphate and/or prostaglandin E2, it is possible that the cell-growth inhibitory effect of interferon is mediated through the "second messenger" system.

Physical, chemical and serological properties of C-type virus associated with transplantable rat Thurzo-Svee leukemia.

Cells of rat Thurzo-Svee leukemia produce C-type virus. Viral particles are shown to contain high-molecular weight RNA and RNA-dependent DNA polymerase the virus possesses mammalian gs-3 antigen and rat species-specific gs-1 antigen and thus appears to be of rat origin.

Interaction of oncornaviral proteins separated by SDS-PAGE with antibodies in immunodiffusion.