bluuebunny/crossref_metadata_2025 huggingface dataset:
Serological detection of a polyoma‐tumor‐associated membrane antigen
Authors: Klein George , Ehlin Barbro , Witz Isaac
Published: February 2007

Syngeneic antisera raised against three polyoma tumors, SEYF‐a, SESO and SEWE, of strain ABY, A and ASW origin, respectively, contain antibodies directed against multiple specificities. One specificity is cross‐reactive for the three polyoma tumors, but appears to be absent from a large variety of other tumors tested. Other, more “public” antigens are shared with a variety of other tumors of viral or non‐viral origin. Five different public specificities of this type have been demonstrated and to some extent defined. Since the SEWE ascites tumor, with the shortest passage history, is much less liable to induce antibodies against the public specificities than the long‐passaged SEYF‐a and SESO, it is likely that the corresponding antigenic determinants arise as a result of passenger virus pick‐up during continued passage, or are due to secondary cytogenetic changes.
Cell‐mediated mutagenesis in cultured chinese hamster cells by polycyclic hydrocarbons: Mutagenicity and DNA reaction related to carcinogenicity in a series of compounds
Authors: Wigley Caroline B. , Newbold Robert F. , Amos Jacqueline , Brookes Peter
Published: February 2007

Three potycyclic hydrocarbons, benz(a)anthracene, 3‐methylcholanthrene and 7,12‐dimethyl‐benz(a)anthracene, have been studied in a cell‐mediated mutagenesis system using BHK 21 cells to metabolize the hydrocarbons and V‐79 cells as targets for detecting induced cytotoxicity and mutation. In large‐scale experiments, the DNA of V‐79 cells was analyzed by column chromatography to determine the nature and true extent of reaction of hydrocarbons with deoxyribonucleosides. Products with DNA formed by the two carcinogenic compounds were qualitatively very similar to those reported to occur in vivo and in primary cell cultures. Binding indices were calculated from the tritium content of DNA‐hydrocarbon products, related to overall metabolism, for these two compounds together with benzo(a)pyrene and 7‐methylbenz(a)‐anthracene using data from a previous study. These values reflected differences in carcinogenic potency between the compounds. Induced mutation frequencies were related to the extent of DNA reaction with each compound. At equivalent extents of DNA reaction with hydrocarbon products, levels of induced mutation were not significantly different.
Carcinogenic action of low‐dose cyclophosphamide given orally to sprague‐dawley rats in a lifetime experiment
Authors: Schmähl D. , Habs M.
Published: February 2007

In a lifelong experiment Sprague‐Dawley rats received cyclophosphamide (CP) in drinking water. Daily doses of 2.5 (I), 1.25 (II), 0.63 (III), and 0.31 (IV) mg/kg body weight were given to groups of 40 male and 40 female rats five times a week. The median survival time (MST) of treated rats proved to be dose‐dependent. In rats treated with dose I the MST was 638 days for males and 642 for females, in those given dose IV it was 906 days for males and 934 days for females. The percentage of control animals with malignant tumors was 11% for males and 15% for females. The corresponding figures for CP‐treated animals ranged from 32 to 43% for male rats and from 30 to 35% for females. At doses I, II, and III CP proved to be carcinogenic (p vs control <0.05). No carcinomas of the urinary bladder were found in controls but one female showed a benign papilloma of the bladder. However, 17 CP‐treated rats died with carcinomas of the urinary bladder and, remarkably, only one of these was a female. In addition, 18 male and 10 female animals showed benign tumors of the same organotropy. No leukemia was diagnosed in controls, but in CP‐treated rats leukemia was found in 8 male and 11 female animals. These findings support the evidence emerging from case reports in humans showing an increased risk of cancer of the urinary bladder as well as of leukemia in patients treated with CP.
Idiopathic mammary tumors in BALB/c mice
Authors: Moore Dan H. , Sarkar Nurul H. , Holben Jane A. , Sheffiel Joel B.
Published: February 2007

A colony of BALB/c mice consisting of two sublines with a high incidence of mammary tumors was examined for the presence of a mammary tumor virus (MuMTV). The mammary tumor incidences in the two sublines were 18% and 35% at average tumor age 19–20 months. Over a period of 8 years, their milk at third to tenth lactations were monitored for the presence of MuMTV antigen, and the milk and tumors were examined for the presence of B particles. Neither antigen nor B particles were found. Milk and tumor extracts from the higher mammary tumor line were also assayed for MuMTV bioactivity by intraperitoneal inoculation of weanling C57BL, BALB/c, and Rlllf females. No response was obtained, except possibly in Rlllf. Both the MuMTV antigen incidence and the tumor incidence in inoculated Rlllf mice were somewhat elevated over controls. The question remains unanswered as to whether there is an active MuMTV in our colony of tumor‐bearing BALB/c mice and, if there is, whether it is associated with B particles.
Assessment of the use of the Salmonella mutagenesis assay to determine the influence of antioxidants on carcinogen‐induced mutagenesis
Authors: Rosin Miriam P. , Stich H. F.
Published: February 2007

The Salmonella mutagenesis assay was used to study the influence of antioxidants on the mutagenic activities of carcinogens. The assay allowed us to determine which antioxidant would affect a carcinogen's in vitro mutagenic activity as well as to estimate the relative effectiveness of each antioxidant as a carcinogen inhibitor. Antioxidants studied included cysteamine, disulfiram, butylated hydroxyanisole, propyl gal late, sodium selenite, sodium bisulfite, α‐tocopherol succinate and sodium ascorbate. The mutagenic activity of N‐methyl‐N'‐nitro‐N‐nitrosoguanidine was most effectively inhibited by cysteamine and sodium bisulfite with selenite, propyl gallate and sodium ascorbate being only slightly less effective. Propyl gal late, selenite and cysteamine had a similar ability to inhibit N‐acetoxy‐2‐acetylaminofluorene‐induced mutagenesis, whereas the addition of sodium bisulfite, sodium ascorbate and disulfiram had no detectable inhibitory effect on this carcinogen. Butylated hydroxyanisole and α‐tocopherol succinate did not affect the mutagenic activity of either carcinogen. It was also observed that dimethyl sulfoxide, when used as a solvent, could significantly affect the measurement of an antioxidant's efficiency as an inhibitor of carcinogen‐induced mutagenesis. The results obtained indicate the necessity of studying an antioxidant's effect on numerous carcinogens prior to drawing any conclusions as to the potential use of the antioxidant as a carcinogen inhibitor.
Increased monocyte‐mediated cytostasis of lymphoid cell lines in breast and lung cancer patients
Authors: Jerrells Thomas R. , Dean Jack H. , Richardson Gary , Cannon Grace B. , Herberman Ronald B.
Published: February 2007

Peripheral blood mononuclear cells of most normal adults and patients with breast or lung cancer were found to inhibit [3H]thymidine uptake by lymphoid cell lines in a growth inhibition assay. At effector target cell ratios between 5:1 and 20:1, lung cancer patients and breast cancer patients, when compared to normal individuals, demonstrated significantly greater inhibition of [3H] thymidine uptake by a human lymphoid cell line (F‐265). The effector cells were adherent and were probably monocytes. Sephadex G‐10 column passage or adherence to plastic removed most growth‐inhibitory activity. Adherent cells recovered from plastic flasks (88–94% monocytes) were strongly growth‐inhibitory. Lung cancer patients receiving BCG immunotherapy were found to have an apparently increased activity compared to patients not treated with BCG. The possible mediation of the growth inhibition by release of prostaglandins was suggested by the reduced cytostatic effects in the presence of indomethacin. Growth‐inhibitory activity was not species‐restricted, since human effector cells and also effector cells from tumor‐bearing mice were reactive against the human target cell and against a murine lymphoma line (RBL‐5). Natural killer (NK) cells did not appear to contribute appreciably to the observed cytostasis, since the levels of their activities did not correlate, and human NK cells are non‐adherent and have little reactivity against F‐265 or RBL‐5. The inhibition of [3H]thymidine uptake by target cells was demonstrated to be a good reflection of actual inhibition of proliferation, since incubation of adherent cells from cancer patients with F‐265 resulted in similar degrees of reduction in the number of target cells and in [3H]thymidine uptake.
Demonstration of placental alkaline phosphatase in human breast cancer
Authors: Wada H. Garrett , Shindelman Jeffrey E. , Ortmeyer Ann E. , Sussman Howard H.
Published: February 2007

The screening of a series of 11 metastatic breast tumors for the presence of the placental isoenzyme of alkaline phosphatase (EC 3.1.3.1) by RIA revealed one strong producer. The alkaline phosphatase of this tumor was characterized with respect to its immunochemical cross‐reactivity, inhibition by L‐phenylalanine and levamisole, subunit molecular weight (Mr) and isoelectric point (pl) in two‐dimensional electrophoresis, and one‐dimensional peptide map. In all parameters of the characterization, the tumor alkaline phosphatase was similar to placental alkaline phosphatase, except for subunit molecular weight which was slightly lower (60,000 versus 64,000 for the placental isoenzyme). No strong placental alkaline phosphatase producers were found among 16 primary tumors examined by RIA. The screening of patients' sera for the placental alkaline phosphatase using RIA indicated elevated levels over post‐menopausal controls in 20% of the metastatic patients. Only 3% of the primary patients had elevated serum levels. These results suggest that the placental isoenzyme of alkaline phosphatase may be a useful tumor marker for recurrent breast cancer.
Differential inducibility of Epstein‐Barr virus in cloned, non‐producer raji cells
Authors: Bister Klaus , Yamamoto Naoki , Hausen Harald Zur
Published: February 2007

Cells of the human lymphoblastoid non‐producer line Raji were cloned in soft agar. Individual colonies were isolated and analyzed for their inducibility of the Epstein‐Barr virus‐associated early antigen (EA). The induction of EA by the tumor promoter TPA varied among the different cell clones. Clones with very high and very low inducibility of the resident Epstein‐Barr virus genome were further analyzed. Constant differences in the inducibility of EA were observed after activation by tumor promoters, 5‐iododeoxyuridine or antibodies to human IgM. Induction of EA synthesis by super‐infection with Epstein‐Barr virus from the P3HR‐1 line, however, did not vary among the clones tested. No differences in expression of the Epstein‐Barr virus‐associated nuclear antigen (EBNA) were noted in cells of clones with high or low susceptibility to EA induction. DNA reassociation kinetics demonstrated that Raji cells with high susceptibility to EA induction contained a significantly higher number of Epstein‐Barr virus genome equivalents per cell than cells with low susceptibility. Treatment of Raji cells with the tumor promoter TPA did not change the ratio of Epstein‐Barr virus‐specific DNA to cellular DNA.
Tumour‐related antigen specificities associated with 3‐methylcholanthrene‐treated rat embryo cells
Authors: Embleton M. J. , Baldwin R. W.
Published: February 2007

Rat embryo cells were treated in vitro for 18 h with 10 üg/ml 3‐methylcholanthrene (MCA). Syngeneic male rats were immunized with several inocula of treated cells to prepare antisera which were screened for membrane immunofluorescence reactivity against panels of established chemically‐induced syngeneic rat tumours. Three separate anti‐serum pools raised against MCA‐treated cells reacted with certain chemically‐induced tumours, whereas antisera to control (DMSO‐treated) cells were completely negative. The reactions observed were reproducible and highly specific for particular target tumours. Absorption studies indicated that each antiserum contained antibodies to several different antigens, present on different tumours. Antiserum prepared against extranuclear membrane from MCA‐treated cells, rather than intact MCA‐treated cells, was negative. This suggests that the antibody responses were directed against antigens arising subsequently to MCA treatment and injection into syngeneic hosts. It is postulated that carcinogen treatment results in the acquisition of multiple neoantigens among a treated cell population, which represent an early change in a sequence of events leading to malignant transformation.
Elevated titer of antibodies to simian sarcoma virus envelope antigen (gp70) and normal response to influenza virus in untreated danish Hodgkin's patients
Authors: Ebbesen P. , Due C. , Hesse J. , Kurth R. , Noble G. R. , Gallagher R. , Voller A. , Jensen G.
Published: February 2007

Untreated Danish Hodgkin's disease (HD) patients and paired age‐ and sex‐matched controls were tested for serum antibodies to Epstein‐Barr virus (EBV), six strains of influenza virus and Simian sarcoma virus/Simian sarcoma‐associated virus [SSV(SSAV)] antigens. HD sera showed significantly elevated titers against EBV and both increased incidence and mean titer of antibodies to the envelope glycoprotein of SSV(SSAV), whereas testing against the influenza viruses revealed no differences between HD and controls. A focus reduction assay demonstrated a low incidence in HD and controls of sera with neutralizing effects against SSV(SSAV) and the “baboon” C‐type virus component of the human HL‐23 virus complex, which seemed coupled to HL‐A type W19.
Demonstration of antibody‐associated cellular cytotoxicity in patients with acute myelogenous leukemia before and after chemotherapy
Authors: Fäldt R. , Ankerst J.
Published: February 2007

This study demonstrates that a cytotoxic serum reactivity not requiring the presence of complement appears in the sera of patients with acute myelogenous leukemia. The reaction is detected upon short‐term incubation of sera in vitro with autochthonous mononuclear white blood cells from peripheral venous blood of patients at the acute stage of the disease. This reactivity was demonstrated in 18/18 patients. Generally, the cytotoxicity was low in patients at the acute stage of the disease, but increased after chemotherapy and reached the highest level at the onset of clinical remission or just before. No cytotoxicity could be demonstrated against autochthonous remission white blood cells. The serum activity could be absorbed and eluted from protein A‐Sepharose CL‐4B and was recovered in the 7S‐fraction of the sera after gel filtration on Sephadex G‐200 and ion exchange chromatography. This indicates that the demonstrated cytotoxicity is due to immunoglobulins of IgG‐class. It is believed that Fc‐receptor‐bearing cells present in the target cell preparations function as effector cells. The reaction is designated antibody‐associated cellular cytotoxicity (AACC).
Herpesvirus papio: State and properties of intracellular viral DNA in baboon lymphoblastoid cell lines
Authors: Falk Lawrence , Lindahl Tomas , Bjursell Gunnar , Klein George
Published: February 2007

Herpesvirus papio (HVP) is an indigenous B‐lymphotropic virus of baboons (Papio sp.) present in latent form in baboon lymphoblastoid cell lines. It shares cross‐reacting viral capsid and early antigens with the Epstein‐Barr virus (EBV), and HVP DNA and EBV DNA show partial sequence homology. EBV‐specific complementary RNA was employed here as a probe to investigate the physical state of the HVP DNA component in baboon lymphoblastoid cells after fractionation of cellular DNA by density gradient centrifugation. Five virus‐producing cultures contained both free and integrated HVP DNA sequences while one non‐producing cell line had two or three viral genome equivalents per cell in an apparently integrated form. Further analysis of one virus‐producing line showed that the free HVP DNA fraction was composed of both linear and circular viral DNA. Contour length measurements of HVP circular DNA molecules by electron microscopy revealed that they were similar in length to the EBV circular DNA present in human lymphoblastoid cells.
Tumor metastases and cell‐mediated immunity in a model system in DBA/2 mice. V. Transfer of protective immunity with H‐2 identical immune T cells from B10.D2 mice
Authors: Schirrmacher V.
Published: February 2007

Evidence is presented for the existence of immune T lymphocytes which have protective activity in vivo against the lethal effects of a metastasizing tumor. ESb, the metastasizing tumor cell line of our model system, which is highly malignant in syngeneic DBA/2 mice, can be rejected when transplanted into B10.D2 mice. Since B10.D2 and DBA/2 mice are identical at the H‐2 complex, cells could be transferred from the tumor‐resistant into the susceptible strain to determine whether they could confer protective immunity in a syngeneic environment containing disseminated ESb tumor cells. Protective immunity against ESb could be transferred into DBA/2 with spleen cells but not with ascites fluid from B10.D2 mice preimmunized against the ESb tumor cells. B10.D2 spleen cells taken between 6 and 22 days after tumor transplantation had protective immunity, while cells taken from animals 3 days after tumor transplantation, or from normal animals, had no significant protective effect. The cells in B10.D2 immune spleens with protective activity were sensitive to treatment with anti‐theta serum and complement and did not adhere to nylon‐wool columns. Such nylon‐wool column‐passed cells which were enriched for T lymphocytes had a higher protective activity then the unfractionated cells. DBA/2 mice which received viable ESb tumor cells subcutaneously on day 0 could be protected by intravenous inoculation of B10.D2 immune spleen cells only when these were given after the tumor cells (day +1, +3, +5, +7), not when given before (day −3 or −1). The mechanisms of protective immunity against tumor metastasis and the significance of our findings for completely syngeneic tumor systems will be discussed.
Actinomycin D restores in vivo sensitivity to differentiation induction of non‐differentiating mouse myeloid leukemia cells
Authors: Okabe Junko , Honma Yoshio , Hayashi Moriaki , Hozumi Motoo
Published: February 2007

Resistant mouse myeloid leukemia cells could not be induced to differentiate in vitro into mature macrophages and granulocytes by incubation with ascitic fluid or dexamethasone as inducer. Neither could endogenous inducers acting on resistant cells maintained in a diffusion chamber in syngeneic SL mice induce differentiation. However, when resistant cells were pretreated in vitro with low doses of actinomycin D they became sensitive to inducer in vitro or in vivo. The concentration of actinomycin D effective for this effect did not induce differentiation. The effect of actinomycin D was not due to inhibition of cell growth, since sensitivity was not observed when resistant cells were pretreated with the growth inhibitor 5‐fluorodeoxyuridine. When resistant cells were kept in a diffusion chamber in mice injected with low doses of actinomycin D they showed significant differentiation, suggesting that the in vivo effect of actinomycin D is partly attributable to sensitization of the resistant cells to endogenous inducers.
Suppression of lymphokine production by macrophages infiltrating murine virus‐induced tumors
Authors: Varesio L. , Herberman R. B. , Gerson J. M. , Holden H. T.
Published: February 2007

Immune spleen cells from mice injected with murine sarcoma virus (MSV) can produce migration inhibition factor (MIF) in vitro after stimulation with intact tumor cells. We have now found that this effector function can be regulated by suppressor macrophages present in the tumor. The cells from the tumor (CfT) exert a strong suppressive effect even after treatment with anti‐Thy 1.2 plus complement but lose this capacity if adherent or phagocytic cells are removed, suggesting that the macrophage is the suppressor cell. The effects of the suppressor cells were exerted on a proliferation‐independent function of the lymphocytes, since MIF production, as well as its suppression, occurred even after proliferation of the lymphocytes was blocked by mitomycin‐C. The implications of these findings are that macrophages can suppress some early events involved in the activation of lymphocytes by antigen and that they do so through a mechanism that does not relate to the proliferation of the cells.
Structure of tumor antigen on hybrid cells between mouse mammary ascites tumor and mouse fibroblast L cells
Authors: Kubota Koichi
Published: February 2007

Somatic cell hybrids between mouse fibroblast L cells and MM2 mouse mammary ascites tumor grown in BALB/c mice were isolated and the structures of tumor‐associated surface antigen of the hybrid cells, and parental MM2 and mouse L cells were investigated by the methods of radioiodination of membrane proteins, immunoprecipitation with a specific antiserum against tumor‐associated surface antigens of MM2 tumor (anti‐MM2 serum), and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Two molecules of 105,000 and 76,000 daltons were detected on the MM2 cell surface, but no MM2 tumor antigen was detected on the mouse L cells. On the hybrids between these two kinds of cells, in addition to the two MM2 tumor antigens, molecules of 48,000–51,000 and 12,000 daltons were observed. On Sendai‐virus‐infected mouse L cells only a molecule of 68,000 daltons was detected by the anti‐MM2 serum, and furthermore this molecule was also detected by normal mouse serum, indicating that antibodies against Sendai virus were contaminating in both the anti‐MM2 and normal mouse sera used, and thus the molecules detected on the hybrid cells were distinguishable from possible viral components of Sendai virus on the hybrid cells. The results indicate that somatic cell hybrids between mouse L cells and MM2 tumor grown in BALB/c mice expressed on their cell surface the molecules that were not exposed on either parent cell. The experiments comparing newly detected molecules with the H‐2 antigen suggested that they were similar to H‐2 in their electrophoretic pattern.
Partial characterization of an antigen from a human myeloma cell and its reactivity with an anti‐myeloma cell serum
Authors: Krueger Robert G. , Hilton Pamela
Published: February 2007

This report describes studies carried out in an attempt to define the antibody specificity of a rabbit antiserum generated to the RPMI 8226 line of human myeloma cells and then isolate and characterize the antigen. The antiserum reacted to a significantly higher titer in a quantitative semi‐micro complement fixation assay with RPMI 8226 cells as compared to the RPMI 4098 line of human lymphocytes or normal human bone‐marrow cells, particularly after absorption with RPMI 4098 cells. A similar difference in reactivity was also noted for cell‐free lysates of the three different types of cells. A variety of different procedures were carried out to attempt to solubilize the antigens of the RPMI 8226 cell. Of the procedures tried, deoxycholate treatment of sonicated or freeze‐thaw extracts, 3 M KCI, autolysis and papain digestion were found to solubilize antigens from RPMI 8226 cells that reacted with anti‐RPMI 8226 cell serum absorbed with RPMI 4098 cells. Further, the solubilized RPMI 8226 cell antigens did not react with an antiserum to RPMI 4098 cells. Components solubilized from RPMI 4098 cells by similar procedures did not react with the absorbed anti‐RPMI 8226 cell serum to a significant titer. The initial studies carried out to characterize the components solubilized from the RPMI 8226 cell revealed that they were recovered in the included volume after gel filtration on Sephadex G‐200 and that this material consisted of three proteins with approximate molecular weights of 66,000, 55,000 and 31,000 daltons as estimated by electrophoresis on SDS‐acrylamide gels. These results indicate that the RPMI 8226 line of human myeloma cells possesses antigens not found on the RPMI 4098 line of human lymphocytes that can be solubilized and that react with an antiserum generated to intact RPMI 8226 cells.
Effect of parity regimen on the rate of occurrence of mammary tumors in a, C3H, and RIII mice
Authors: Moore Dan H. , Holben Jane A.
Published: February 2007

The occurrence rates of mammary tumors as affected by breeding regimen (early in life, late, continuous, or not at all) in A, RIII, and C3H mice were observed. The response to the breeding regimen was different in each of the three strains. The C3H stock was affected least, although the tumor occurrence rate was slower in virgins. In both A and RIII, only one litter at puberty resulted in the tumors occurring over the greatest age range; and in RIII mice, the occurrence rate and the mean tumor age were similar to those of the virgins. Normal continuous breeding caused the earliest tumors in all three strains, although in RIII mice, breeding after 18 weeks of age also caused very early tumors. The response of RIII strain to parity variations was more like that of humans than was the response of either of the other strains. Removal of the milk‐transmitted virus from these strains by foster‐nursing resulted in vastly different mammary tumor occurrence rates, the quantitative changes being different in each mouse strain.
Rapid release of fibronectin from human lung fibroblasts by biologically active phorbol esters
Authors: Keski‐Oja Jorma , Shoyab Mohammed , de Larco Joseph E. , Todaro George J.
Published: February 2007

A sensitive radioimmunoassay technique has been used to study the effects of several phorbol esters on their ability to release fibronectin from cultured human lung fibroblasts into medium. The biologically active phorbol esters studied rapidly released fibronectin from cells into medium, with concomitant changes in the cellular morphology within 2 h. The quantity of fibronectin released was dose‐, time‐ and promoter‐dependent. The earliest release of fibronectin was seen within 30 min of onset of the incubation. Alterations in membrane topology elicited by phorbol esters appear to be responsible for the rapid release of fibronectin molecules from cells into the medium.
Decreased sensitivity to interferon associated with in vitro transformation of X‐ray‐transformed C3H/10T1/2 cells
Authors: Brouty‐Boyé Danièle , Gresser Ion , Baldwin Claire
Published: February 2007

We have compared the interferon sensitivity of parental 10T1/2 cells, having a phenotype characteristic of normal cells, with that of transformed cells isolated after X‐irradiation or treatment with methylcholanthrene. Transformed cells were 10‐ to 20‐fold less sensitive than the parental untransformed cells to the antiviral action of interferon and were also less sensitive to the inhibitory effect of interferon on cell multiplication. The decreased sensitivity of these cells to interferon is a useful marker of the transformed phenotype.
“NK‐like” cytotoxicity of human lymphocytes cultured in media containing fetal bovine serum
Authors: Golub Sidney H. , Golightly Marc G. , Zielske John V.
Published: February 2007

Human peripheral blood lymphocytes (PBL) were found to be highly cytotoxic to a human malignant melanoma target cell line after the PBL were cultured in medium supplemented with 20% fetal bovine serum (FBS). The effector cells had surface markers similar to those of non‐cultured NK effectors against melanoma targets. Both NK (without culture) and the culture‐induced cytotoxic effectors had Fcγ receptors, lacked Fcμ receptors and were either heterogeneous for E receptors or had low‐affinity E receptors. Cells required to generate the FBS response were sensitive to anti‐T serum plus complement, passed through a nylon‐fiber column, formed E rosettes, but lacked detectable receptors for the Fc portions of either IgG or IgM. These results suggest that events causing activation of T cells such as culture of PBL in FBS‐containing medium, result in the augmentation of NK activity.
Chromosome breaking activity of human feces and its enhancement by transition metals
Authors: Stich Hans F. , Kuhnlein Urs
Published: February 2007

Chloroform‐methanol extracts from human fecal samples were found to contain compounds which induce chromosome aberrations in Chinese hamster ovary cells. The induction of chromosome aberrations is stimulated by Cu2+ or Mn2+ and inhibited by Fe2+ or Fe3+. Addition of catalase to the fecal extract or the mixture of fecal extract and Mn2+ reduced the frequency of chromosome aberrations. These properties are indicative of hydroxyradical producing agents.
Biological and biochemical observations on isolates of EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas
Authors: Crawford D. H. , Epstein M. A. , Bornkamm G. W. , Achong B. G. , Finerty S. , Thompson J. L.
Published: February 2007

Foetal, adult seronegative, and cotton‐top marmoset lymphocytes have been transformed into cell lines by EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas. The nature of the cell lines was checked by karyotyping and by light and electron microscopy, and the presence of the EB virus genome was demonstrated by immunofluorescence tests. Immunofluorescence also showed the incidence of EB virus‐producing cells in each line and this was checked by electron microscopy and the use of a lymphocyte transformation assay. Two foetal‐derived lines did not produce virus spontaneously, could not be activated with various inducers, and were found by DNA reassociation kinetics to carry only small numbers of genome copies per cell. An adult‐derived line produced virus, could be activated to produce more, and provided enough infectivity to transform marmoset cells. The resulting marmoset line made profuse transforming virus; it thus provides the first abundant source of NPC‐derived infectious EB virus for comparative studies. The results are discussed in relation to the interactions with comparable target cells of EB virus from normal individuals and from patients with other diseases.
Induction of reproductive system tumors in mice by N6‐(methylnitroso)‐adenosine and a tumorigenic effect of its combined precursors
Authors: Anderson Lucy M. , Giner‐Sorolla Alfredo , Greenbaum Jeffrey H. , Last‐Barney Kathleen , Budinger John M.
Published: February 2007

Interaction of the naturally‐occurring nucleoside, N6‐methyl adenosine, with nitrite, a reaction that occurs readily under acidic conditions, results in the formation of a nitrosamine, N6‐(methylnitroso) adenosine [m6(NO)Ado]. This nitrosamine was given in the drinking water (1 mM solution) of non‐inbred Swiss mice from 3 weeks of age until death. It caused a significant increase in the incidence of primary lung tumors, compared with controls. It also induced reproductive tract tumors in 80% of the exposed females, including mammary tumors in 60% and uterine tumors in 25%. The precursors of m6(NO) Ado, m6Ado and nitrite, did not elevate tumor incidence when given singly, but when administered together resulted in a significant increase in numbers of lung tumors in the males. The nitrosamine base, N6‐(methylnitroso)adenine, was found to be a less potent carcinogen than m6(NO)Ado, causing lung tumors only in males and possibly a few mammary tumors in females. These results indicate the in vivo formation of a carcinogen from m6Ado and nitrite, and show that m6(NO)Ado induces neoplasms in the reproductive system of mice, an unusual target for a N‐nitroso carcinogen.
C. parvum treatment of transplanted rat tumours of spontaneous origin
Authors: Willmott N. , Pimm M. V. , Baldwin R. W.
Published: February 2007

C. parvum (Wellcome CN6134) has been examined for suppression of a range of transplanted rat tumours of spontaneous origin. With five tumours (three mammary carcinomas and two fibrosarcomas) growth of comparatively high cell inocula (with respect to the minimum for growth in control rats) was suppressed by admixture with the vaccine. Equivalent dry weights of Glaxo, Pasteur or Connaught BCGs were relatively ineffective. Intralesional injection of C. parvum into three established tumours (two mammary carcinomas and one fibrosarcoma) retarded development of only one, the mammary carcinoma Sp4. With three mammary carcinomas and one fibrosarcoma, active specific immune stimulation with vaccines of viable or irradiated cells admixed with C. parvum was again consistently effective only with carcinoma Sp4, and this tumour was also susceptible to intradermal but not intravenous treatment with C. parvum alone.
Transformation of feline embryo cells in culture by a chemical carcinogen
Authors: Rhim J. S. , Nelson‐Rees W. A. , Essex M.
Published: February 2007

A feline embryo cell line was treated in vitro with various levels of 7,12‐dimethylbenz[α]anthracene (DMBA) or dimethyl sulfoxide (control). Repeat treatment of DMBA only induced in vitro transformation of feline embryo cells following clonal growth and selection. The morphologically altered cells formed large cell aggregates and grew in this aggregate form when suspended in liquid growth medium above an agar base, formed colonies in soft agar, and grew to high saturation densities. However, no progressively growing tumors were produced when cells were inoculated into nude athymic mice. The transformed lines were negative for feline oncornavirus‐associated cell membrane antigen (FOCMA).
Absence of ecotropic or recombinant murine leukaemia virus in preleukaemic and leukaemic X‐irradiated NZB mice
Authors: Harvey Jennifer J. , Tuffrey Maureen , Holmes H. C. , East June
Published: February 2007

NZB mice X‐irradiated with a single dose of 630 R when they were 1‐month old developed a high incidence of histologically defined lymphocytic leukaemia 8–25 weeks later. We have screened for murine leukaemia viruses (MuLV) in the lymphoid tissues of 8 of these leukaemic mice, and in 8 “preleukaemic”, apparently healthy NZBs, killed 1 month post irradiation. Xenotropic, but not ecotropic or recombinant MuLV, was detected by in vitro co‐cultivation of bone marrow, spleen and thymus with selectively permissive cell lines, followed by the immunofluorescence test for MuLV gs antigen, and the XC test. Our results are not consistent, therefore, with the concept that the factor causing the leukaemias was an oncogenic virus activated by X‐irradiation.
Light chain isotype‐associated suppression of normal plasma cell numbers in patients with multiple myeloma
Authors: Leonard R. C. F. , MacLennan I. C. M. , Smart Y. , Vanhegan R. I. , Cuzick J. ,   In conjuction with the Medical Rsearch Council's Working Party for Leukaemia in Adults and The Oxford Lymphoma Group
Published: February 2007

The number of plasma cells in the lamina propria of the gut has been assessed in patients with multiple myeloma and other B‐cell neoplasms. The total number of these plasma cells was reduced in most patients with myelomatosis and one‐third of patients with lymphoplasmacytoid tumours. This reduction was not, however, seen in patients with other neoplasms of B‐cell origin, although hypogamma‐globulinaemia was common to all groups of patients. The depletion of gut plasma cell numbers was not uniform in myelomatosis patients. They showed selective loss of plasma cells with the same light chain isotype as that produced by the neoplastic clone.
Effect of anti‐mouse type‐1 interferon globulin on the evolution of moloney sarcoma virus induced disease in mice
Authors: Inglot Anna D. , Inglot Olga , Zóltowska Albina , Oleszak Emilia
Published: February 2007

The prolonged administration of potent sheep anti‐mouse type‐1 interferon globulin (anti‐IF IgG) had a marked potentiating effect on Moloney sarcoma virus (MSV) infection in mice. The extent of resistance to the MSV‐induced disease was age‐related. In 4‐week‐old BALB/c mice, anti‐IF IgG consistently induced 70–80% mortality due to the progression of early or late tumours and erythro‐leukaemia, whereas mortality of control mice was significantly lower. The same effect was obtained in 1‐year‐old BALB/c mice. However, in 4‐week‐old C57BL/6 or 6‐week‐old BALB/c mice, anti‐IF IgG enhanced only the growth of early tumours but had no effect on their regression. Antigenic stimulation with normal sheep globulin suppressed the growth of early tumours in suckling BALB/c or C57BL/6 mice and enhanced the evolution of late MSV‐induced disease in older mice.
Binding of anti‐tumor immunoglobulins and their daunomycin conjugates to the tumor and its metastases. In vitro and in vivo studies with lewis lung carcinoma
Authors: Hurwitz Esther , Schechter Bilha , Arnon Ruth , Sela Michael
Published: February 2007

The present study was undertaken in order to evaluate the possibility of using anti‐tumor anti‐bodies as specific carriers of chemotherapeutic drugs to tumor metastases. Xenogeneic and syngeneic antisera were prepared against a metastasizing C57BL tumor, the Lewis lung carcinoma (3LL). The binding of absorbed xenogeneic and syngeneic anti‐3LL sera or their Ig fractions to 3LL tumor cells was assayed by direct and indirect methods. Antisera prepared against tumor cells from a local growth reacted to a similar extent with cells obtained from the local tumor and with those obtained from the lung metastases. Radioiodinated immunoglobulins from syngeneic antisera injected into mice bearing metastases localized preferentially in metastasis‐bearing lungs as compared to several other organs tested. No such preferential uptake was observed either in mice bearing metastases injected with iodinated normal Ig or in normal mice injected with iodinated anti‐3LL Ig. This relative accumulation in the metastasis‐bearing lungs was observed 3–4 days after the inoculation, when the whole Ig fraction was used, whereas a specific antibody‐enriched preparation localized as early as 24 h after injection. Daunomycin—anti‐3LL‐Ig conjugates were effective inhibitors of tumor cells from both local and the metastatic growths. They were more active than either the free drug or drug conjugates of normal Ig, in in vitro assays.
Malignant behaviour of three adenovirus‐2‐transformed brain cell lines and their methyl cellulose‐selected sub‐clones
Authors: Gallimore Phillip H. , McDougall James K. , Chen Lan Bo
Published: February 2007

Three adenovirus‐2‐transformed rat embryo brain cell lines and their methylcellulose‐selected subclones were examined for fibronectin expression, anchorage‐independent growth, saturation density, T antigen expression and morphology. Tumorigenicity studies were carried out on newborn and ATS immunosuppressed syngeneic rats and congenitally athymic nude mice. With one exception the methyl‐cellulose sub‐clones contained significantly fewer fibronectin‐positive cells than the parent lines; a number of sub‐clones contained no fibronectin‐positive cells. Methylcellulose selection did not always alter cell morphology, saturation density or anchorage‐independent growth as compared with parent lines. However, the methylcellulose sub‐clones were considerably more malignant than the parent cell lines as measured by invasion and metastasis in nude mice. No in vitro characteristic correlated with malignant behaviour.
Analysis of chromosomal proteins of fractionated chromatin from rat liver and transplantable hepatocellular carcinomas
Authors: Rodriguez Lewis V. , Klein Kenneth K. , Amoruso Marie , Becker Frederick F.
Published: February 2007

The chromosomal proteins from a number of transplantable hepatocellular carcinomas (THC) induced by a single carcinogen or its derivatives and varying greatly in their growth rates were examined by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Before extraction and analysis of proteins, chromatin from hepatomas, as well as from normal and regenerating liver was fractionated into rapidly and slowly sedimenting gradient components. Ten non‐histone chromosomal proteins (NHCP) present in the tumors and ranging in molecular weight from 220,000 to 55,000, were absent from normal liver. Further, each rapidly growing tumor possessed more non‐histone protein bands in the most rapidly sedimenting chromatin fractions than did corresponding, slowly growing tumor fractions. A number of single protein occurrences common only to normal liver and/or rapidly or slowly growing tumors were also found. In contrast, NHCP banding patterns of rapidly growing 70% hepatectomized rat liver were identical to those of non‐dividing liver. Of particular interest was the finding that the prototypic “minimal deviation tumor” 9618A varied more in its NHCP‐banding pattern when compared to liver than did those tumors which were rapidly growing and poorly differentiated. These studies represent an initial attempt at seeking NHCP which might be uniquely related to the malignant process.
The localization of Hodgkin's disease in lymph nodes. A study with immunohistological, enzyme histochemical and rosetting techniques on frozen sections
Authors: Poppema S. , Elema J. D. , Halie M. R.
Published: February 2007

Lymphoid tissue of 51 patients with Hodgkin's disease was studied with immunohistological, enzyme histochemical and rosetting techniques for the detection of B and T cells in frozen sections. In lymph nodes of patients with lymphocyte predominance type of Hodgkin's disease, the majority of the lymphocytes in the involved areas were normal B lymphocytes of polyclonal origin. This was also true for nodular sclerosis cases with a predominance of lymphocytes. Surrounding Sternberg‐Reed cells small clusters of T lymphocytes could be demonstrated. In mixed cellularity and also in nodular sclerosis with a mixed cellular pattern only small residual areas of B lymphocytes were presènt, whereas relatively large numbers of T lymphocytes were found in the involved areas. In lymphocyte depletion B lymphocytes were scarce and T lymphocytes were present in small number. It is concluded that different patterns of lymphocyte population can be discerned in the subtypes of Hodgkin's disease. A predominance of B lymphocytes is found in cases with lymphocyte predominance and thus is a prognostic favourable sign. A predominance of T lymphocytes as found in cases with a mixed cellular pattern with or without nodular sclerosis is therefore not a favourable sign in general but may indicate progressive disease. The possible reasons for the presence of large numbers of B or T lymphocytes in lymphoid tissue affected by Hodgkin's disease are discussed.
Breast cancer in black American women
Authors: Austin Harland , Cole Philip , Wynder Ernst
Published: February 2007

A case‐control study of breast cancer among Black American women was conducted in seven hospitals in New York City from 1969 to 1975. Results are reported for 127 cases and 317 controls. Compared to women with a first birth before age 19, those with a first birth after 25 had a relative incidence rate for breast cancer of 3.8 and 2.2 for the pre‐ and postmenopausal age‐groups, respectively. Compared to nulliparous women, parous women had a relative incidence rate of 0.6 for premenopausal and 0.7 for postmenopausal women. The incidence rate of breast cancer for women with a menopause after age 49 was estimated to be 3.1 times that of women with a menopause before age 45. Thus, the known risk factors for breast cancer among Whites are also related to the etiology of the disease among Blacks. The incidence rate of breast cancer has increased among younger Blacks since 1947 and is now similar to that among younger Whites. However, among older women, the incidence rate is still appreciably higher for Whites. The most likely explanation of this pattern is that Black women born since about 1925 are being exposed at the same frequency as White women to the causes of breast cancer.
Humoral and cellular immunity to paternal antigens in trophoblastic neoplasia
Authors: Shaw A. R. E. , Dasgupta M. K. , Kovithavongs T. , Johny K. V. , Leriche J. C. , Dossetor J. B. , McPherson T. A.
Published: February 2007

Antibody‐dependent cellular cytotoxicity (ADCC) was employed to detect and characterize an unusually high‐titered antibody to a paternal HLA antigen in a patient with gestational choriocarcinoma. Choriocarcinoma is a trophoblastic neoplasm of embryonic origin, and therefore genetically competent to express paternal histocompatibility antigens. However, normal human trophoblast is reported to lack HLA antigens. The demonstration of a high‐titre antibody to a paternal antigen is of interest for two reasons: it suggests that HLA antigens develop in trophoblast as a consequence of malignancy, and might therefore constitute a marker for neoplasia. Secondly, it indicates that a highly immunogenic antigen of tumor origin is provoking a humoral response, but that the disease is progressing in the face of such immunity. The antibody is distinguishable from that provoked by normal pregnancy in three ways. It is of exceedingly high titre (> 1:32,000 against paternal lymphoblast targets); it is monospecific for the paternal HLA B locus antigen 12; and it demonstrates a pronounced prozone indicative of the presence of immune complexes (ICs). Post‐partum sera from multiparous women frequently contain HLA antibodies demonstrable in ADCC. However, titres are comparatively low, the antibodies are not monospecific, but recognize HLA and other (Ia) antigens, and they do not show a marked prozone, or the presence of immune complexes. ICs were indeed demonstrable at a concentration of >25 μg/ml (aggregated human gamma globulin equivalents) by a modified Raji cell technique. Histological examination of the uterine tumor following hysterectomy revealed a high degree of mononuclear cell infiltration, suggestive of cell‐mediated immunity. The patient was quite capable of generating cytotoxic T‐cells to paternal lymphocytes on challenge in mixed lymphocyte culture, indicating that no general anergy or suppressor function was present. The possibility that suppression might be limited to the single B locus specificity sensitizing the patient's humoral response was not investigated. Since immune complexes interfere with both ADCC cytotoxicity and T‐cell cytotoxicity it is suggested that they might contribute to the lack of resistance to a demonstrably immunogenic allograft.
Anti‐tumor potential of retinoic acid: Stimulation of immune mediated effectors
Authors: Patek Paul Q. , Collins John Leslie , Yogeeswaran Ganesa , Dennert Gunther
Published: February 2007

Data are presented on the effects of retinoic acid (RA) treatment on the in vivo growth of tumors in two mouse strains. Inhibition of tumor growth as a result of systemic RA injection was observed in three out of seven tumor models. Using adult thymectomized, lethally irradiated and fetal liver (A × TFL) reconstituted mice, we found that inhibition of tumor growth is not due to direct toxic effects of RA but rather appears to be the result of stimulation of thymus‐dependent immune‐mediated effectors able to suppress tumor growth. Results suggest that only strongly immunogenic tumors are sensitive to in vivo retinoid inhibition.