bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective cytotoxicity of tunicamycin for transformed cells
Authors: Olden Kenneth , Pratt Robert M. , Yamada Kenneth M. 
Published: February 2007

AbstractWe have studied the effects of tunicamycin, an inhibitor of dolichol pyrophosphate‐dependent glycosylation of proteins, on the viability of transformed and non‐transformed fibroblasts in culture. We have shown that a low concentration of tunicamycin (0.05 μg/ml or 5 × 10−8 M) is cytotoxic toward a variety of transformed cell lines, including virally or chemically transformed fibroblasts from chick embryo, rat kidney, human lung, and mouse. The corresponding non‐transformed cell lines were resistant to the same and a 10‐fold higher concentration of tunicamycin. However, transformed permanent cell lines were also found to be resistant to tunicamycin. The relationship between transformation and tunicamycin cytotoxicity was strengthened by the finding that chick embryo fibroblasts infected by the temperature‐sensitive viral mutants ts68 or T5 are killed by the drug only at the temperature at which transformation is expressed. The LD50 for sensitive transformed cell lines ranged from 0.02 to 0.034 μ/ml tunicamycin. Maximal cytotoxic effects to transformed cells were produced at tunicamycin concentrations which only slightly inhibited protein synthesis in non‐transformed cells (17–22% in 24 h). There was a good correlation between the susceptibility of transformed cells to tunicamycin cytotoxicity and their sensitivity to tunicamycin inhibition of protein glycosylation, 2‐deoxy‐D‐glucose transport, and glucose metabolism. These results indicate that tunicamycin interferes with some cellular process critical for the survival of many transformed cells but not of non‐transformed cells. We speculate that the cytotoxicity of this drug towards transformed cells may result from impaired rates of nutrient transport, although other mechanisms are possible. Tunicamycin may, therefore, be therapeutically useful as an anti‐tumor agent to selectively kill certain types of malignant cells, while sparing non‐transformed cells.
Inhibition of mammary tumorigenesis in GR mice with 2‐bromo‐α‐ergocryptine
Authors: Welsch Clifford W. , Goodrich‐Smith Margaret , Brown Carolyn K. , Wilson Mark 
Published: February 2007

AbstractA high incidence of mammary tumors is found in multiparous GR mice during the 2nd and 3rd pregnancies and in nulliparous GR mice treated with estrone/progesterone. The purpose of this study was to determine if prolactin is a contributing hormone in the genesis of these neoplasms. In one series of experiments, 238 15‐week‐old nulliparous GR mice were treated with estrone (drinking water, 0.5 mg/liter) plus progesterone (30 mg progesterone pellet with cholesterol, implanted SC once monthly) for a period of 13 weeks. Half of these mice were injected SC once daily with 100 μg of the prolactin‐suppressing drug 2‐bromo‐α‐ergocryptine (CB‐154) for the duration of hormone treatment, and the other half were injected SC once daily with 0.9% NaCl solution (controls). In another series of experiments, 87 pregnant GR mice were divided into two groups and injected SC once daily from day 7 to 21 of pregnancy with 0.9% NaCl solution (controls) or CB‐154 (100 μg/mouse). In the first series, the numbers of mice with mammary tumors and total number of mammary tumors were: controls, 58/119 (49%) and 73; CB‐154 treatment, 34/119 (29%) and 37, respectively. In the second series, the numbers were: controls, 39/44 (89%) and 73; CB‐154 treatment, 24/43 (56%) and 43, respectively. In both studies, CB‐154 treatment significantly (p<0.05–0.005) reduced the percentage of mice with mammary tumors and total number of mammary tumors. These results provide evidence that prolactin is a contributing hormone in the genesis of estrone/progesterone and pregnancy‐induced mammary tumors in female GR mice.
Large interindividual variations in metabolism of benzo(α)pyrene by peripheral lung tissue from lung cancer patients
Authors: Cohen Gerald M. , Mehta Rekha , Meredith‐Brown M. 
Published: February 2007

AbstractA very large variation (44‐fold) was observed in the ability of short‐term organ cultures of peripheral lung tissue from lung‐cancer patients to metabolize the environmental carcinogen benzo(a)pyrene to organic solvent‐soluble metabolites. The amounts of benzo(a)pyrene (2 μM) metabolized ranged from little (1%) to almost total (96.2%) metabolism within 24 h of culture. Previous work by Kellerman et al. (1973) has suggested a relationship between susceptibility to lung cancer and the inducibility of aryl hydrocarbon hydroxylase activity in cultured human lymphocytes. The metabolic fate of carcinogenic polycyclic aromatic hydrocarbons in the respiratory tract in vivo is undoubtedly more closely mimicked by short‐term organ culture of human lung than by cultured lymphocytes. Thus the very wide interindividual variation observed in pulmonary metabolism of benzo(a)pyrene in this study and the large variations in covalent binding to human bronchial DNA observed by Harris et al. (1976) strongly suggest that there may be little basis for screening humans for variations in lymphocyte aryl hydrocarbon hydroxylase activity as a means of assessing their susceptibility to lung cancer.
Cytotoxicity against the K562 erythroleukemia cell line by human natural killer (NK) cells which do not bear free Fc receptors for IgG
Authors: Kay H. David , Fagnani Roberto , Bonnard Guy D. 
Published: February 2007

AbstractWhen Fc receptors (FcR) on normal human peripheral blood lymphocytes were induced to modulate by overnight (18 h) incubation in the presence of soluble or particulate immune complexes, the natural killer (NK) activity of the effector lymphocyte suspension, as measured against the K562 erythroleukemia cell line, was significantly, but only partially, inhibited. The NK activity which remained was always strong, and was not significantly inhibited by inclusion of antigen‐antibody complexes in the cytotoxicity assay, nor was it further depleted by adsorbing the modulated cells on plastic surfaces coated with immobilized antigen‐antibody complexes. Antibody‐dependent cell‐mediated cytotoxicity (ADCC) against rabbit antibody‐sensitized Chang liver cells was totally abrogated following the modulation process, and could not be restored by exposure of modulated effector cells to trypsin, indicating that the FcR had actually been shed and were not merely being blocked with immune complexes. Although freshly isolated peripheral blood lymphocytes active in natural (or “spontaneous”) cytotoxicity have been shown to bear FcR, our data indicate that NK activity against the K562 cell line can be effectively mediated by NK cells which have lost their FcR. This supports the concept that NK activity against K562 is independent of FcR, and, therefore, of IgG.
Cytolytic activity of macrophages isolated from primary murine sarcoma virus (MSV)‐induced tumors
Authors: Taniyama Tadayoshi , Holden Howard T. 
Published: February 2007

AbstractMacrophages isolated from regressing or progressing tumors induced by murine sarcoma virus (MSV) were tested for cytolytic activity in an 18‐h 51Cr release assay. Macrophages from the tumors of mice injected 14 days earlier with stocks of MSV‐producing regressor or progressor tumors had comparable levels of cytotoxicity. However, macrophages from the progressively growing tumors, 50–65 days after the inoculation with the progressor virus, had lower levels of cytotoxicity than those from the regressing tumors (day 14). On the other hand, macrophages from progressively growing MSV tumors (day 14) in nude mice had little or no detectable cytolytic activity. In a fractionation study, using the 1‐g velocity sedimentation technique, cells from regressing tumors (day 14) showed at least two peaks of cytolytic activity, one at about 4 mm/h and another at 6–7 mm/h, while cells from the progressing tumors (day 60) had only one peak of cytolytic activity, at about 4 mm/h. In contrast, none of the cell fractions of tumors from nude mice (day 14) showed cytolytic activity. Since bacterial lipopolysaccharide (LPS) has been shown to augment the cytolytic activity of primed macrophages, its effect on cells from MSV tumors was evaluated. Cytolytic activity of the cells from regressing or progressing tumors that had pre‐existing cytolytic activity was augmented by the addition of LPS during the assay period, but LPS treatment did not activate inactive fractions or change the distribution patterns of the cytolytic activity in fractions from 1‐g velocity sedimentation.
Analysis of the expression of H‐2 and H‐2‐linked antigens on mammary tumor cells
Authors: Snoek Margriet , Démant Peter 
Published: February 2007

AbstractThe products of the recently discovered H‐2L locus were expressed on BALB/c mammary tumor cells and behaved as histocompatibility antigens, in contrast to the products of H‐2 linked loci (Qa‐loci) that did not influence the acceptance or rejection of tumor transplants.
Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti‐interferon serum. VI. Polyoma virus infection
Authors: Gresser Ion , Maury Chantal , Kress Chantal , Blangy Daniel , Maunoury Marie‐Thérèse 
Published: February 2007

AbstractWe have determined the effect of a single injection of potent sheep anti‐mouse interferon globulin on polyoma‐virus‐induced early runting disease and tumor formation in Swiss mice. When newborn mice were injected with ≥9 × 106 PFU of polyoma virus, 16% (7/44) of mice runted and died in contrast to 96% (45/47) of mice injected with virus and anti‐interferon globulin. Likewise, a greater percentage of mice injected with lower doses of virus and anti‐interferon globulin developed tumors than did control virus‐injected mice. These results suggest that interferon is an important factor in determining the susceptibility of newborn mice to polyoma virus.
Loss of alpha‐fetoprotein in rat hepatoma culture cells
Authors: Yoo Tai‐June , Kuo Chao Ying , Patil Shivanand R. , Kim Untae , Cancilla Pasquale , Ackerman Larry D. 
Published: February 2007

AbstractThe production of alpha‐fetoprotein (AFP) by cultured rat Morris hepatoma 7777 hepatoma cells was studied. Initially, in vitro, rat hepatoma tumor cells synthesized and released AFP into the culture medium. As subculturing progressed, however, their ability to produce AFP diminished. After 8 months of in vitro cultivation, a non‐AFP‐producing tumor cell line had not lost its tumorigenicity and produced a solid tumor when injected into two groups of Buffalo rats. New tumors derived from tissue culture cells have shown significantly lower levels of serum AFP than the in vivo tumor line. However, another subline of this hepatoma tissue culture (7777 Iowa) did not lose its ability to produce AFP after 1 year of in vitro culture. Electron microscopy demonstrated no morphological change when the two different lines (AFP‐producing and non‐AFP‐producing) were compared. Chromosomal analysis in these cell lines revealed that the non‐AFP‐producing line (7777 TC) had 42% cells with a diploid or near‐diploid complement whereas the AFP‐producing (7777 Iowa) line showed a greatly variable aneuploidy number with 45% of the cells near tetraploidy. The reason for the virtual loss of AFP production or the different response of this tumor cell in the rat hepatoma culture remains unknown. Our studies and others indicate that, though AFP is an oncofetal antigen and a gene product of tumor cells, the control mechanism of AFP production could be an epiphenomenon of tumor cell and not related to the control of tumor growth and differentiation.
Cell surface sialylation of glycoproteins and glycosphingolipids in cultured metastatic variant rna‐virus transformed non‐producer BALB/c 3T3 cell lines
Authors: Yogeeswaran Ganesa , Sebastian Henry , Stein Barry S. 
Published: February 2007

AbstractThe sialic acid composition and the display of cell surface sialyl components of several metastatic variant RNA‐virus‐transformed non‐producer BALB/c 3T3 have been studied in culture. The following observations have been made concerning the sialyl components in these lines: (1) the compositions of whole‐cell total, protein‐bound and lipid‐bound sialic acid were not appreciably different; (2) the surface sialic acid studied using the neuraminidase‐galactose oxidase method and metabolic labelling followed by neuraminidase hydrolysis showed a positive correlation with the metastatic properties of these lines; (3) the degree of surface sialylation determined by galactose oxidase—sodium borotritide labelling of neuraminidasetreated and untreated cells revealed that 44–89% of exposed galactose and/or N‐acetyl galactosamine residues of total cell‐surface saccharides were sialylated in highly and intermediately metastatic lines as compared with 11–30% in the poorly and non‐metastatic lines; (4) the cell surface glycoproteins and glycosphingolipids contributed equally well in their degree of sialylation and there was a positive correlation with the metastatic properties of the cells in vivo; (5) the cell surface proteins labelled by the lactoperoxidase‐catalyzed iodination technique, followed by gel electrophoresis, showed some minor differences between metastatic variant lines. However, glycoproteins detected by the galactose oxidase labelling of neuraminidase‐treated and untreated cells showed major differences in composition between the metastatic variant lines. The study of four highly metastatic lines has shown that the cells of these lines were enriched in several sialyl‐glycoproteins, whereas three non‐tumorigenic lines and two poorly metastatic or non‐metastatic lines contained unsialylated glycoproteins. The results indicate an enhancement of the degree of sialylation of surface glycoconjugates accompanying the metastatic process in RNA‐virus‐transformed mouse lines.
Characterization of a type‐C virus produced by co‐cultures of human leukemic bone‐marrow and fetal canine thymus cells
Authors: Smith R. Guy , Nooter Kees , Bentvelzen Peter , Robert‐Guroff M. , Harewood K. , Reitz M. S. , Lee Sin Ai , Gallo R. C. 
Published: February 2007

AbstractThe putative human helper virus SKA‐21/A204V, isolated by Nooter et aal. in 1977 from human leukemic bone‐marrow cells following co‐culture with normal fetal canine thymus cells, Cf2th, has been characterized with respect to its major viral core protein, reverse transcriptase, and nucleic acid sequences. The results of these analyses show that this virus is not distinguishable from the woolly monkey type‐C virus, SSAV‐1, by the techniques employed.
Augmentation of cell‐mediated cytotoxicity to a rat lymphoma. I. Stimulation of non‐T‐cell cytotoxicity in vivo by tumour cells
Authors: Dawkins H. J. S. , Shellam G. R. 
Published: February 2007

AbstractThe injection of a syngeneic Gross‐virus‐induced lymphoma into W/Fu rats induced peaks of cytotoxicity in the spleen attributable to non‐T cells and T cells 3 and 10 days later, respectively. The conditions required for augmenting the cytotoxicity of the non‐T cells in various lymphoid compartments (shown elsewhere to closely resemble NK cells) were analysed using the ip and iv routes of inoculation and a variety of tumour cells including those normally susceptible or resistant to lysis by NK cells in vitro. Using an ip inoculation of W/FuG‐1 cells (a tumour susceptible to lysis by NK cells), a short‐lived, 3‐fold increase in cytotoxicity was observed in the spleen at day 3 and a 5‐fold increase in the PEC at day 5. Cytotoxicity in other lymphoid organs remained unchanged. Tumours resistant to lysis by NK cells also stimulated cytotoxicity in the spleen or PEC, although the effect depended on the dose and route of inoculation used, and depression of cytotoxicity was observed under some conditions.
Augmentation of cell‐mediated cytotoxicity to a rat lymphoma. II. Characterization of the non‐T cytotoxic cells stimulated in vivo by tumour cells as natural killer cells
Authors: Dawkins H. J. S. , Shellam G. R. 
Published: February 2007

AbstractA variety of tumours injected into rats were found to rapidly stimulate cytotoxicity which was similar to naturally‐occurring cytotoxicity of normal rats. Cytotoxic cells from the spleen and peritoneal cavity closely resembled NK cells in their lytic specificity and cell‐surface characteristics. Thus, although cytotoxicity could be stimulated “non‐specifically” with tumours which were resistant to lysis in vitro by NK cells, the cytotoxic cells exhibited patterns of specificity against a panel of target cells in direct lysis or competitive inhibition assays which were similar to those of NK cells from normal rats. These cells also closely resembled NK cells in being largely non‐adherent, non‐T cells, and in exhibiting a similar heterogeneity in the expression of Fc receptors. Thus, cytotoxicity which was augmented shortly after tumour inoculation appeared to be attributable to NK cells. However, whilst the majority of NK cells from normal or tumour‐inoculated rats shared these properties, significant heterogeneity was observed Minor populations of cytotoxic cells were adherent, were lysed by a heterologous anti‐T‐cell antiserum and complement and did not express an Fc receptor, although it was not determined whether the same subpopulation possessed all three characteristics.
Tumor metastases and cell‐mediated immunity in a model system in DBA/2 mice. VI. Similar specificity patterns of protective anti‐tumor immunity in vivo and of cytolytic T cells in vitro
Authors: Bosslet K. , Schirrmacher V. , Shantz G. 
Published: February 2007

AbstractIn an attempt to analyze mechanisms of immunity against tumor metastases, protective anti‐tumor immunity in vivo was compared with cytotoxic T‐cell activity in vitro in a well‐defined syngeneic tumor model system. The system consists of a chemically induced parental tumor cell line (Eb) with little or no metastatic potential and a spontaneous variant thereof (ESb) with pronounced metastatic properties. Tumor protection experiments revealed the presence of tumor‐associated transplantation antigens (TATAs) on both Eb and ESb tumor cells. TATAs of Eb and ESb were found to be distinct and non‐cross‐reactive. One of several unrelated tumors, however, RL♂1, expressed TATAs which cross‐reacted with those of Eb. Protective immunity against the non‐metastasizing tumor was much stronger than that against the metastasizing variant. Furthermore, the optimal procedures for induction of immunity in vivo were strikingly different for each tumor. Tumor‐specific cytotoxic T lymphocytes (CTLs) were obtained after sensitization in vivo with viable tumor cells and restimulation in vitro for 4–5 days with mitomycin‐C‐treated autologous tumor cells. Both anti‐Eb and anti‐ESb CTLs showed high cytolytic activity in a 4‐h 51Cr release assay against the autologous tumor lines. The target antigens recognized by these cells were similar to the TATAs as defined in the protection experiments. (1) The target antigens of Eb and ESb were distinct and non‐cross‐reactive. (2) Only one of 14 unrelated syngeneic and allogeneic tumors expressed a target antigen which cross‐reacted with that of Eb. (3) This tumor was the radiation‐induced BALB/c lymphoma RL♂1 which also cross‐reacted at the level of the TATAs. The correlations between protective immunity obtained in vivo and cytolytic T cells induced in vitro suggest that cytolytic T cells can recognize TATAs and may thus play an important role in the establishment of protective immunity.
Effect of sodium butyrate on the antiviral and anticellular action of interferon in normal and MSV‐transformed cells
Authors: Bourgeade M. F. , Chany C. 
Published: February 2007

AbstractSodium butyrate enhances the antiviral and anti‐cellular action of interferon in MSV‐transformed cells but has no such effect in normal cells. The increased sensitivity could be mediated at least partially by the butyrate‐induced elaboration of the microtubule and microfilament network.
Molecular heterogeneity of alpha‐fetoprotein secreted by primary and transplantable hepatocellular carcinomas
Authors: Kelleher Philip C. , Smith Carol J. 
Published: February 2007

AbstractDue to differences in carbohydrate content, rat AFP exhibits concanavalin A (Con A)‐binding heterogeneity. In order to investigate the control of the glycosylation of AFP synthesized by malignant cells, the patterns of AFP Con A affinity molecular variants secreted by sixteen 3′‐methyl‐4‐dimethyl‐aminoazobenzene‐induced primary hepatocellular carcinomas were followed sequentially during growth of the primary tumors through establishment as transplantable hepatocellular carcinomas. Fourteen of the transplantable tumors showed stable patterns of serum AFP Con A affinity molecular variants. Five of these 14 tumors secreted patterns of AFP Con A affinity molecular variants similar to the patterns found in the sera of the rats bearing the primary tumor of origin; the remainder of the tumors secreted an AFP Con A affinity molecular variant pattern which bore no relationship to that of the primary hepatocellular carcinoma of origin. Two of the transplantable hepatocellular carcinomas did not secrete stable proportions of AFP Con A affinity molecular variants during the 2‐year study. In 14 transplantable hepatoma lines the patterns of AFP Con A affinity molecular variants throughout successive transplant generations were significantly different from the pattern found in newborn rat serum. The stability of AFP Con A affinity molecular variant secretion by transplantable hepatocellular carcinomas indicates that the control of glycosylation of AFP and perhaps of other proteins is a heritable phenotypic property of these tumors and is consistent with other observations that the metabolic activities of transplantable hepatocellular carcinomas are constant over a period of years.
The differentiation of clonal rat yolk SAC tumor cell lines cultivated with dibutyryl‐cyclic 3′, 5′‐adenosine monophosphate
Authors: Tsukada Yutaka , Hibi Nozomu , Sakashita Shigeo , Abe Kazuhiro , Hirai Hidematsu 
Published: February 2007

AbstractFive rat yolk sac tumor cell lines were cloned from a yolk sac tumor line which originally arose following fetectomy. The doubling time of each of the cloned tumor lines was about 50 h. All of the cloned tumor cell lines synthesized and secreted AFP and albumin but there was a gradual decrease in the synthesis of these proteins during serial passage. The cells formed clusters which looked like vitelline ducts or the parietal yolk sac and they also had basement membranes which closely resembled Reichert's membrane. When the cloned cell lines were cultivated in the presence of 1 mM dibutyryl cyclic‐AMP, myotube‐like and neuron‐like cells appeared. Acetylcholine esterase and creatine phosphokinase activity were present when myotube‐like cells were present whereas acetylcholine esterase activity predominated when neuron‐like cells were present.
Tritiated thymidine as a broad spectrum initiator in transplacental two‐stage carcinogenesis, with phorbol as promoter
Authors: Armuth Vlasta , Berenblum Isaac 
Published: February 2007

AbstractA single subcutaneous injection of 200 μCi [3H] thymidine into pregnant BALB/c mice, followed by intraperitoneal injections of phorbol, twice weekly for 25 weeks, in the offspring, resulted in higher tumour development in the lungs and livers of male and, to a lesser extent, of female offspring, than in their untreated littermates. The difference in over‐all tumour incidence was statistically significant, but the increases of the individual tumour types were only of borderline significance. Slight carcinogenic activity of [3H]thymidine alone was observed in the mothers, and in the offspring, without phorbol treatment. The results suggest the possibility of using [3H]thymidine as a broad spectrum initiator for transplacental two‐stage carcinogenicity studies to determine the organ specificity of different promoting agents.