The effect of combined treatment of hypoxic L5178Y-R and L5178Y-S cells with lidocaine and X-rays.

Combination of lidocaine (6 mg/ml) and X-rays was used for treatment of two strains of L5178Y lymphoma cells under hypoxic conditions. The strains L5178Y-S (radiosensitive) and L5178Y-R (radioresistant) differ in radiosensitivity by a factor of about 1.4 whereas they are equally sensitive to lidocaine. For combined treatment of L5178Y-R cells the enhancement ratio was 1.4 and for that of L5178Y-S cells 1.0. Cell partition between two aqueous polymer phases [Dextran T500 and poly(ethylene glycol) 6000] does reflect neither viability nor the commitment of treated cells to interphase or reproductive death.

Decrease in pyrrole-2-carboxylic acid excretion during lung cancer disease.

A statistically significant decrease of pyrrole-2-carboxylic acid in urine was observed in lung cancer of stage I (TNM classification) when compared to that of healthy miners (chronically exposed to radiation) from the uranium industry. The difference vanishes in stage II of the disease and reappears in stage III. While nonmalignant lung diseases (bronchopneumonia and chronic bronchitis) do not interfer in the stage I with the drop of pyrrole-2-carboxylic acid excretion, in stage III of lung cancer the decrease is less pronounced and cannot be differentiated from that found in bronchopneumonia or chronic bronchitis.

Lymphnodal metastases from unknown primary tumors.

Prognosis and adequate therapy of lymphnodal metastases from unknown tumors are still uncertain. At the Milan Cancer Institute 71 patients with neoplastic adenopathies of unknown origin were hospitalized between 1965 and 1979. Men were 45 and women 26 with a M/F ratio of 1.7: 1. Most of patients were aged 51-70 years. Laterocervical adenopathies were the more frequent, followed by supraclavicular, axillary, inguinal, submandibular and retroperitoneal ones. In 11 cases the primary tumor was subsequently found (3 cases in tongue, 3 in rhinopharynx. 2 in lung. 2 in breast and 1 in thyroid). Of the remaining 60 cases, only histologic diagnosis of the metastasis was available and the primary tumor has never been found. Squamous cell carcinoma was the most frequent histologic type, followed by adenocarcinoma, undifferentiated carcinoma and malignant melanoma. No significant relationship between histologic types and lymphnodal sites could be demonstrated. In different cases treated with all possible combined therapies (surgery, chemotherapy and radiotherapy), no correlation between survival and therapy was possible. 35 patients (58.3%) were dead 18 months after diagnosis. No significant correlation between survival and histology was either shown. The natural history of these tumors remains unclear and any specific therapy cannot be proposed to be scheduled in such cases.

The thrombo-embolic disease as a paraneoplastic syndrome.

Out of 4139 patients autopsied, 629 had the thrombo-embolic disease (15.2%). 548 patients suffered from various malignancies, and among them 102 (19.9%) had the thrombo-embolic disease as well. Only 5 patients with the thrombo-embolic disease had an occult malignoma. The increased incidence of the thrombo-embolic disease in patients suffering from various types of malignancies is statistically significant (0.05 less than p greater than 0.02). The interceptibility of the paraneoplastic thrombo-embolic disease at the hospital departments is very low when compared to necropsy (about 3%) but, on the other hand, in more than one half of all cases studied it represents the first clinical symptoms of a malignoma, though rarely evaluated correctly. The clinico-pathologic aspects of the paraneoplastic thrombo-embolic disease are discussed.

Induction of gamma-glutamyl transpeptidase positive cells by benzo(a)pyrene in embryonic rat tongue cells in culture.

The utility of gamma-glutamyl transpeptidase as a histochemical marker to study the carcinogen induced changes in primary epithelial and fibroblasts mixed cell cultures of embryonic rat tongue by benzo(a)pyrene (BP) was explored. It was observed that at low BP concentrations selectively cells with fibroblasts morphology were intensely stained for GGT. At relatively higher concentrations of BP all the cells with fibroblasts morphology were eliminated and GGT positive areas were observed in cells with epithelial cell morphology. A carcinogen dose-related cell specificity for GGT activity was observed.

Modulation of tumor incidence by oncofetal products in a syngeneic hepatoma cell-spleen cell model.

An experimental model is described for analysis of cellular and molecular mechanisms involved in the modulation of tumorigenicity by syngeneic lymphoid cells and oncofetal products in vivo. The effect of mouse amniotic fluid (AF) and alpha-fetoprotein (AFP) from this fluid and from serum, free or bound to estrogens, upon the growth of a syngeneic hepatoma was examined in mice transferred with syngeneic spleen cells from hepatoma-bearing donors. Intraperitoneal transfer of spleen cells from hepatoma-bearing into normal syngeneic mice, either tended to stimulate or to inhibit tumor growth in the latter depending on the length of time elapsed between tumor-transplantation in the spleen-cell donor and their sacrifice for spleen excision. For example, only the spleen cells obtained on day 14 and 21 following tumor transplantation protected the recipients from tumor growth. When these protective cells were mixed with hepatoma cells from a low incidence line, and the mixture injected subcutaneously, tumor incidence increased (tumor-promotion effect) rather than the contrary. AF was immunosuppressive inasmuch as it amplified the tumor-promotion effect of the spleen cells. On the other hand, purified AFP from sera of hepatoma bearing mice abolished this tumor-promotion effect.

Reaction of various human normal and leukemic cells and cells of different cell lines with rabbit antisera prepared against membrane fraction of B and T cell lines.

Serological analysis of human membrane antigens have been performed using rabbit xenosera against membrane fraction obtained from different cells (B cell lines: RAJI, RAMOS, DAUDI, UHKT-2: T cell line: MOLT-3, as well as normal pooled lymphocytes). The direct cytotoxicity testing demonstrated that xenogeneic rabbit B lymphoid antisera mediated a significant reaction in the complement-dependent cytotoxicity assay against an antigenic determinant on normal peripheral blood B lymphocytes but not against T lymphocytes and granulocytes. Moreover, these xenoantisera react with antigenic specificities present on the CLL leukocytes, on some AML myeloblasts, on the hairy cells, on majority of ALL and CML blasts, but not on eosinophilic leukocytes and on T lymphocytes from peripheral blood of patients with CLL, ALL, AML, and CML in remission. These xenoantisera react with antigenic specificities present on the cells of cultured lymphoid cell lines of B type, but not on cells of T cell lines.

Effect of exogenous immunogenic RNA on the antibody synthesis in rat transplantable lymphosarcoma cells.

Cytoplasmic and nuclear RNA were isolated from sheep red cells immunized rat and mouse spleens. Rat spleen nuclear RNA was fractionated in the following steps: 1. thermal fractionation according to Georgiev, 2. hydroxylapatite chromatography of thermal fraction, 3. agar gel electrophoresis of saline hydroxylapatite fractions. The effect of all these fractions on hemolysin synthesis in rat transplantable lymphosarcoma cells was studied. It was shown that the total cytoplasmic RNA of rat and mouse spleen and some nuclear RNA fractions of rat spleen are able to induce hemolysin synthesis. The antibody synthesis induced in vitro by addition of rat spleen RNA can be proved in about 10-12 cell generations at subsequent transplantations of the tumor. The 4S nuclear RNA, as well as high molecular RNA are apt to induce antibody synthesis. The mechanism of 4S RNA action can not be the same as that of mRNA. Concluding our experimental data and those available in the literature we assume that there are two different mechanisms of immunogenic exogenous RNA activity in transfer of the biological information in immunogenesis: that of mRNA information transfer and that of deblockation of corresponding genes in recipient cells.

In vitro induction of chronic myeloid leukemia associated immune reactivity in normal human lymphocytes by xenogeneic immune RNA.

Peripheral blood lymphocytes from normal human donors were treated with immune RNA (IRNA) prepared from lymphoid tissues of guinea pigs immunized with chronic myeloid leukemia (CML) cells, normal leukocytes (WBCs) and normal bone marrow (BM) cells, in order to study whether IRNA can confer specific immunoreactivity on normal lymphocytes. The IRNA treated lymphocytes were further exposed to solubilized membrane antigens from CML cells, normal WBCs and BM cells in a criss-cross fashion. The migration inhibition factor produced by these lymphocytes was tested in an in vitro leukocyte migration inhibition assay using normal leukocytes. The results indicated that IRNA prepared from guinea pigs immunized with all the three cell types could transfer the immune reactivity to normal cells in response to the respective antigens. The WBC IRNA incubated lymphocytes did not react with BM cell and CML cell antigens. A potent transfer of specific reactivity was shown by CML IRNA. IRNA produced against BM cells and CML cells demonstrated considerable cross reactivity perhaps due to shared immature cell antigens.

Biosynthesis of nuclear RNAs during 3'-methyl-4-dimethyl-aminoazobenzene hepatocarcinogenesis and in transplantable rat hepatomas.

The long-term administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) to rats causes marked changes in concentrations and synthesis of nucleic acids in the liver. In the beginning, a decrease in total cellular RNA concentration can be seen. On the other hand, at the stage of tumor onset the concentration of nuclear RNAs in precancerous lesions and hepatomas is elevated. Incorporation of 3H-orotic acid into nuclear RNA after 45 min of in vivo labeling serving as a measure of biosynthesis of nuclear RNAs is markedly decreased when compared to control livers. This decrease takes place from the very beginning of the process and goes on until primary hepatomas arise in which its values are approximately at 10% of those observed in controls. In the present study the problem of the increase of proliferative activity at early stages of carcinogenesis is discussed which is not in correlation with the changes in nuclear RNA biosynthesis.

Ammoniacal silver staining of lymph node cells. I. its potential value for the diagnosis of Hodgkin's disease.

Lymph node biopsy specimens from 76 cases of Hodgkin's disease, 23 non-Hodgkin's lymphomas and 19 reactive affections of lymph nodes were studied. Formalin-fixed and paraffin embedded tissues were stained with hematoxylin and eosin, and post-formalin ammoniacal silver staining was used after BLACK and ANSLEY. The presence of basic protein accumulation in the cytoplasm of both Sternberg and Hodgkin cells was confirmed. To our knowledge it is the first report concerning the presence of these accumulations in the cytoplasma of atypical reticulum cells in Hodgkin's disease and in 3 of 7 cases of reactive follicular hyperplasia, in foreign body giant cells and in some lymphoblasts from 5 cases of Hodgkin's disease. The possibility of using the ammoniacal silver staining for identifying Sternberg cells is discussed. Also, it is proposed that when Sternberg cells are absent, the ammoniacal silver staining pattern of Hodgkin cells in an appropriate histological setting may be very indicative of Hodgkin's disease.

Alteration in lysosome supravital staining as a marker of hydroxyurea-induced cytotoxicity and its modification by radical scavengers in L5178Y cells in culture.

Supravital staining of lysosomal membranes with euchrysine was employed to study hydroxyurea (HU)-induced side toxic effects in L5178Y lymphoblasts in culture. Exposure of cells to 0.1-1.0-10.0 mM HU-induced progressive increase in the proportion of cells without detectable lysosomal fluorescence. This effect preceded the occurrence of non-viable cells, determined by trypan-blue exclusion test. Addition of alpha-tocopherol, acetylsalicylic acid, sodium benzoate or ascorbic acid to the culture medium afforded a concentration-dependent modification of lysosomal response to HU treatment. It is suggested that the fluorescence technique of supravital lysosome staining can be a useful test in studies on the side toxic effects of free radical-forming drugs and their amelioration by radical scavengers.

Inclusion of cisplatinum (cis-DDP, Platidiam, Lachema) into combined chemotherapeutic protocol for the treatment of testicular cancer.

Fifty-seven patients with testicular tumors have been treated with combined chemotherapy (vinblastine, bleomycin and cisplatinum). By evaluation of therapeutic activity and toxic effects it was shown that Platidiam, Lachema, effectivity was identical with the two other cisplatinum preparations used in this study.

Use of monoclonal antibodies against avian retroviral protein p19 for competitive radioimmunoassay and immunodiffusion.

Monoclonal antibodies were used in competitive binding assays to investigate the arrangement of three epitopes on the protein p19 of avian myeloblastosis virus (AMV). It was reasoned that if the epitopes recognized by two monoclonal antibodies are physically close, the binding of one antibody will sterically block the binding of the second; conversely no blocking will occur if the epitopes are sufficiently distant. The results of these competitive binding assays demonstrated the presence of two distinct antigenic sites on the protein p19. Monoclonal antibodies against the protein p19 of AMV were tested also in gel double immunodiffusion. Since the p19 protein has strong tendency to aggregate, it was not surprising, that clear precipitin lines with these monoclonal antibodies were obtained.

Allogenic modification of rat sarcoma cells in vitro by staphylococcal exotoxin.

The effect of toxin preparations from Clostridium welchii and Staphylococcus aureus on the growth of some experimental animal tumor cell lines was investigated. While clostridium toxin exerted considerable cytotoxicity, it did not influence either in vivo or in vitro growth of recovered cells. However, staphylotoxin treated sarcoma cells, while showing normal in vitro growth and metabolism, exhibited decreased growth rates when transplanted into susceptible hosts. This effect was demonstrable even after as many as 10 or more passages in vitro after the toxin treatment. Increased immunogenicity of staphylotoxin treated sarcoma cells was demonstrated by the complement-dependent serum cytotoxicity test. These results indicate that bacterial products, besides cytotoxicity and macrophage stimulation, may exert other effects upon tumor cells, for instance alteration of their immunogenicity and thus influence the tumor growth.

Suppressor cells in melanoma and lung cancer: correlation with the clinical stage.

Mononuclear blood cells from 40 healthy donors, 25 patients with melanoma and 35 patients with lung cancer were tested for suppressor cell activity and response to phytohemagglutinin (PHA). The suppressor cell activity was measured by determining the ability of Mitomycin C (MMC)-treated mononuclear cells from patients and controls to suppress the in vitro response of responder cells to PHA. Mononuclear cells from one healthy donor were stored in liquid nitrogen for use as responder cells. Indomethacin-sensitive suppression was also measured. In both groups of patients the mean values of suppressor cell activity in co-culture were higher than those in control group. When patients were subdivided in groups according to the clinical stage, the level of suppressor cell activity increased with the stage. Indomethacin-sensitive suppression was detected in some patients but the differences between patient and control groups were not statistically proved. An inverse relationship was observed between indomethacin-sensitive suppression and the PHA response.

Murine splenocyte migration inhibition assay I. Detection of differential responses to murine leukemia P388 and its adriamycin-resistant subline P388/ADR.

A direct splenocyte migration inhibition assay system was used to evaluate cellular sensitization in BDF1 mice carrying intraperitoneal transplants of the lymphocytic leukemia, P388, and its adriamycin-resistant subline, P388/ADR. The individual splenocyte populations, PS and PAD (from the mice bearing P388 tumor and its subline, respectively), were tested against the 3 M KCl extracts, S-Ag and R-Ag (of P388 and P388/ADR tumor cells, respectively). The results indicated a gradual development of cellular sensitization against P388 tumors but not P388/ADR tumors. The migration of only PS cells was inhibited by extracts of both the syngeneic tumors in a dose-dependent manner. An extract of an allogeneic tumor, S-180, did not alter the migration of PS cells. The nonresponsive PAD cells, when mixed with the responsive PS cells at a ratio of 1:9, abrogated the latters' response to both the antigens. Such suppression was tumor-related and detected in the spleen 2 days after P388/ADR transplantation. Addition of normal murine splenocytes or P388/ADR tumor cells did not prevent PS cells from responding to the tumor extracts. These results indicated the presence of suppressor cells in the spleens of mice with P388/ADR tumors.

Murine splenocyte migration inhibition assay. II. Characterization of splenic suppressor cells in mice bearing P388/ADR tumor.

Suppressor cells in the spleens of mice bearing i.p. transplants of adriamycin-resistant P388/ADR tumors were detected by their ability to abrogate the response of splenocytes from syngeneic mice bearing i.p. transplants of the parental adriamycin-sensitive P388 tumors, in a mixed splenocyte migration assay system. In further experiments the suppressor cells were found to be enriched after removal of nylonwool-adherent cells. Complete loss of the suppressive activity after exposure of the nylonwool-nonadherent splenocytes to monoclonal antithy 1.2 antibody and complement indicated the T-lineage of the suppressor cells. Furthermore, intracellular synthesis of proteins, but not DNA, was found to be essential for manifestation of the suppressive activity. In addition, the suppressor cells associated with P388/ADR tumors were found to be sensitive to gamma-radiation (5 Gy) and hydrocortisone (3 micrograms/ml).

The World Health Organization. Histological typing of breast tumors.

The WHO Histological Classification of Breast Tumors, published in 1968 has been completely revised. This second edition provides a recommended nomenclature, definitions and code numbers for both tumors and tumor-like lesions. It aims at promoting uniformity in recording and reporting diagnoses in order to facilitate international and other comparisons.

In vitro cultivation of embryonic rat tongue cells--a convenient system for oral carcinogenesis studies.

Fine mince of embryonic rat tongue suspended in medium and transferred to culture vessel adhere immediately to surface. Epithelial and fibroblastic cell outgrowth seen in the first few days was overgrown with fibroblasts later. Evidence is presented that these fibroblasts are sensitive to post-confluence inhibition of division and exhibit several properties of normal fibroblasts including limited lifespan. This system may serve as a simple in vitro model for oral carcinogenesis studies.

Brain tumors in children. Results of treatment in 138 patients.

Tumors of the nervous system are the third most common malignant disease in Cuban children, after leukemia and lymphoma. In 138 patients with the diagnosis of brain tumor results of treatment by surgery and radiation were studied. The survival rate at 1, 3 and 5 years was 50, 40 and 37.6%. The best results were achieved in astrocytomas, mid grain and brain stem tumors and oligodendrogliomas.

Cytotoxicity of lymphocytes and antibodies against autologous tumor cells in patients with myeloid leukemias and preleukemic disorders. I. Blocking activity of gp70 antigens of primate type C viruses.

Cytotoxicity of lymphocytes or antibodies against autologous tumor cells could be demonstrated very frequently in patients with chronic myeloid leukemia, whereas the presence of such cytotoxic activities was very rare in patients with acute myeloid leukemia. Lymphocytes and antibodies cytotoxic against autologous granulocytes were found in persons with potentially preleukemic cytopenic disorders. Control subjects with nonpreleukemic hematological disorders and healthy persons exhibited no cytotoxic activity. In the majority of cases the lymphocyte- or antibody-mediated cytotoxicity could be blocked with gp70 antigen of gibbon ape leukemia virus and baboon endogenous virus.

Murine mammary tumor virus expression during mammary tumorigenesis in ICRC mice.

The expression of murine mammary tumor virus (MuMTV) antigens was examined in the mammary epithelium of strains ICRC and C3H/Jax mice during sequential events leading to mammary tumorigenesis, employing immunoperoxidase technique and competition radioimmunoassays (RIA). The MuMTV antigens could be localized in the lobule alveolar structures of normal, lactating, preneoplastic and neoplastic mammary epithelium as well as in metastatic nodules of mammary tumors of ICRC force breeders. A graded increase in staining reaction was evident with increase in cellularity of the mammary gland due to age and parity. These observations compared well with the quantitation of MuMTV antigens by RIA. The levels of MuMTV antigens in the mammary glands of ICRC mice of different experimental groups were consistently lower than those in C3H/Jax mice. The differential response of the mammary glands to ovariectomy observed in these two strains was reflected in the MuMTV expression.

Soft agar clonogenic assay in human breast cancer.

Relationship between histology, cloning efficiencies and estrogen receptors was studied in the group of breast cancer patient. Mechanical disaggregation gave poor cellular yields since only in 66% cells were ready for the bioassay. Comparison between clonogenic assay, histology and estrogen status of human breast cancer is of a limited value only, because of a small number of patients in our study.

Reactivity of free and coordinated radicals in biology and chemical carcinogenesis. II. Electron transfer from 3,4-benzopyrene to molecular oxygen and to peroxides, and interpretation of ESR signals of the intermediate radicals of oxidation.

Already a trace of oxygen mediates the one-electron transfer from 3,4-benzopyrene (benzo(a)pyrene, BP) to hydrogen peroxide or to tert. butyl hydroperoxide (ROOH), leading in this way to generation of highly reactive HO X, HO2 X or RO X and RO2 X radicals in nonpolar solvents at biological temperatures. At slightly higher concentration of O2 in solution and at moderately elevated temperature (40-60 degrees C) a stable radical pair (HO-BPO X)2 in equilibrium with its diamagnetic dimer of quinone-hydroquinone type is formed. The paradiamagnetic equilibrium of this redox system is reversibly shifted with temperature. At low temperature (up to -40 degrees C) the paramagnetism disappears. The precursor of the radical pair, which can be decomposed, applying a polar solvent, is the keto form of the hydroxy derivative (6-HO-BP) at ambient temperature. According to the study of highly resolved ESR spectra of the primary temporarily formed ion radical pair [BP+ X O-2 X] of BP oxidation in the dark, of the secondary radical pair (HO-BPO X)2 and of the coordinated unhindered phenoxy radicals of hydroxy derivatives BPO X CoIII, the mechanisms of one-electron or of hydrogen-atom transfer from radical intermediates of BP to potential biological targets is discussed.

Survival of patients with advanced ovarian carcinoma treated with Penberol.

The authors report their results of treatment in patients with ovarian carcinoma (stages III and IV, FIGO classification) with the cytostatic Penberol (cis-beta-4-pentoxybenzoyl-beta-bromoacrylic acid), synthesized at the Research Institute for Pharmacy and Biochemistry in Prague. The present communication links on the paper published in 1980. Out of 20 patients treated with Penberol, 11 have responded by a complete remission persisting for 8-55 months; in five of them the remission has not finished as yet. Both in the experiment and in the clinic the behavior of Penberol differs from that of classical cytostatics, and the observations evaluated so far attest to antitumor activity based on inhibition of the cell energetic metabolism.

Incidence of the histologic types of ovarian tumors in Benghazi (Libya) and Poland.

The distribution of histological types of ovarian tumors in two communities with different reproductive experience was compared. 108 cases of ovarian neoplasms diagnozed in Benghazi and 2238 cases collected in Ovarian Tumors Registry in Poland were classified according to the WHO histological typing. The difference in the incidence of histologic types and malignancy was statistically evaluated. Unlike Poland series, in Benghazi germ cell tumors are the most common type of ovarian neoplasms (50% of all reported cases), while the percentage of epithelial tumors accounts for 33.3. This proportion of incidence of epithelial and germ cell tumors in Benghazi is similar to relative frequency of these tumor types noted in teenagers in Europe and the USA. The difference in incidence of the histologic types of ovarian tumors in Benghazi and Poland is probably due to the significantly higher rate of fertility among Libyan women as compared with Polish female population.

Circulating antibodies to the feline leukemia virus and FOCMA in cats.

Presence of antibodies to the structural proteins of the feline leukemia virus and the feline oncornavirus-associated cell membrane antigen FOCMA was analyzed in sera of 120 cats from household environments. In our experiments 35% of the sera tested were positive with the viable cells of FL-74 feline lymphoma cell line. On the other hand, only 5% of the feline sera reacted with FeLV from FL-74 cells in the solid phase RIA. Selected positive sera were analyzed for the presence of antibodies to the viral structural proteins of FeLV and FOCMA in lysates of FL-74 cells by radioimmunoprecipitation. Absorption of the selected sera (reacting with viable FL-74 cells) with disrupted FeLV had a negligible effect on the precipitating activity of the 70000 protein.

Tightly complexed with DNA nonhistone chromatin proteins from hamster Kirkman-Robbins hepatoma.

Two groups of nonhistone chromatin proteins tightly bound to DNA were isolated from hamster liver and Kirkman-Robbins hepatoma with the use of hydroxyapatite columns: 1. NP proteins which can be briefly defined as nonhistone chromatin proteins, nondissociable from DNA in 5 M urea, and 2. a group of proteins nondissociable in 2 M KCl and thus believed to be nonelectrostatically bound to DNA. The proteins were characterized by their amino acid analysis, SDS-polyacrylamide gel electrophoresis and their influence on template activity of DNA. Some differences in electrophoretic patterns and template activity inhibition were found between the latter group of proteins from liver and hepatoma.

Radioprotective and hemodynamic effects of WR-2721 and cystamine in rats: time course studies.

In experiments on rats radioprotective dose of WR-2721 (200 mg/kg) and cystamine (50 mg/kg) exhibited significant protective effects against radiation death during the first hour after their i. m. administration. Gamma rays were delivered with the dose rate of 0.35-0.31 Gy/min in gradually increased doses for the calculation of LD values and relative efficacy of the whole body irradiation. WR-2721 afforded protection with the highest dose reduction factor (DRF) of 1.51, while the best DRF value after cystamine was 1.36. No protection was found when the interval between injection of both protectors and the beginning of irradiation was longer than 60 min. WR-2721 as well as cystamine induced in pentobarbital anesthetized rats significant depression of cardiac output, hypotension and bradycardia immediately after their i. m. injections. The signs of depression of the hemodynamics persisted throughout the 4-hour observation period. Our results indicate that the hemodynamic effects of WR-2721 and of cystamine are not important for their radioprotective actions in rats.