bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous human lymphocyte‐mediated cytotoxicity against tumor target cells. II. Is the complement receptor necessarily present on the killer cells?
Authors: Pross Hugh F. , Baines Malcolm G. , Jondal Mikael
Published: February 2007

The effect of various lymphocyte depletion techniques on SLMC effector cell activity against the cell line K562 could be attributed t o the effects that these procedures had on the proportions of FclC3 receptor‐bearing cells in the preparations. Depletion of cytotoxic activity by removal of Fc receptor‐bearing cells could be augmented by the presence of complement on the 7S‐EA indicator cells used for rosette depletion. Two methods of assessing the presence of surface receptors on cytotoxic cells are presented: (1) linear regression analysis of spontaneous cytotoxicity plotted as a function of the proportions of receptor‐bearing cells remaining after various depletion techniques; and (2) the use of a mathematical formula t o estimate the proportion o f cytotoxic cells with any particular receptor, based on the effects of receptor‐bearing cell depletion. Linear regression analysis of cytotoxicity vs the proportions of SRBC, Fc o r C3 receptor‐bearing cells demonstrated that all cytotoxic cells had the Fc receptor, but that cytotoxicity could s t i l l occur in the absence of cells with the C3 receptor. This indicated that the C3 recepor is not necessary for the demonstration of SLMC activity. The mathematical formula to predict cytotoxicity after depletion of C3 receptor‐bearing lymphocytes showed, however, that a significant proportion of the Fc receptor‐positive killer cells were also C3 receptor‐positive. No direct evidence was found t o support a role for T cells in SLMC, although E rosette depletion resulted in lower than expected cytotoxicity i n view of the number of Fc receptor‐bearing cells remaining in the preparation.
The relative proliferation index as a more sensitive parameter for evaluating lymphoproliferative responses of cancer patients to mitogens and alloantigens
Authors: Dean J. H. , Connor R. , Herberman R. B. , Silva J. , McCoy J. L. , Oldham R. K.
Published: February 2007

Lymphocyte proliferation (LP)6 assays were performed in microculture using the T‐cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A); the T+B cell mitogens, pokeweed mitogen (PWM) and staphylococcal phage lysate (SPL); and a pool of allogeneic stimulating leukocytes in oneway mixed leukocyte cultures (MLC) in lung and breast cancer patients and normal individuals. The resultant data were expressed in three different ways: (1) as mean counts per minute (CPM) of tritiated thymidine incorporation; (2) as a stimulation index (SI) and (3) as a relative proliferation index (RPI). The RPI is defined as the ratio of net CPM (nCPM) in experimental cultures with stimulant (E) minus medium control cultures (C) of a test individual to the mean nCPM of three or more normal individuals examined in the same assay on the same day. These expressions were then compared for their ability to discriminate between LP responses in cancer patients and normal individuals. The RPI value and selected cut‐off values gave the most sensitive measure for the determination of depressed proliferative responses. These analyses demonstrated that lung carcinoma patients were depressed to PHA (50%), MLC (47%), PWM (43%) and Con A (40%). To a lesser degree, breast carcinoma patients were also depressed to MLC (36%), PHA (31%), PWM (27%) and Con A (19%). Our data indicate that the use of the RPI in the analysis of LP response represents an improved method for detecting impaired response of lymphocytes to general mitogens and alloantigens which can consistently reveal immunosuppression in many cancer patients and may be useful for serial monitoring of individual patients.
α‐Fetoprotein‐containing cells in the early stages of liver carcinogenesis induced by 3′‐methyl‐4‐dimethyl‐aminoazobenzene and 2‐acetylaminofluorene
Authors: Tchipysheva T. A. , Guelstein V. I. , Bannikov G. A.
Published: February 2007

The morphology of rat liver cells containing α‐feto‐protein (AFP) during early stages of carcinogenesis induced by 3′methyl‐4‐dimethylaminoazobenzene and 2‐acetylaminofluorene was investigated. Indirect immunofluorescence was used to detect AFP. AFP was not found in the cells of hyperplastic nodules but was present in the cells located in areas of transitional cell proliferation. A large proportion of the AFP‐positive cells formed gland‐like structures. The cells containing AFP were at various levels of differentiation according to morphological criteria. Poorly differentiated, small, basophilic cells were predominant among the AFP‐positive population. The most highly differentiated AFP‐positive cells had the morphology of hepatocytes.
The binding of benzo(a)pyrene and N‐methyl‐N′‐nitro‐n‐nitrosoguanidine to subnuclear fractions of akr mouse embryo cells in culture
Authors: Zytkovicz Thomas H. , Moses Harold L. , Spelsberg Thomas C.
Published: February 2007

The marked localization of a carcinogenic polycyclic aromatic hydrocarbon, benzo(a)pyrene, and its metabolites and a carcinogenic alkylating agent, N‐methyl‐N'‐nitro‐N‐nitrosoguanidine, to a specific subnuclear fraction (fraction I) from AKR‐2B mouse embryo cells in culture is described. Fraction I is isolated by sucrose gradient centrifugation of sheared nuclei from cells exposed to the carcinogens. The association of tritiated benzo(a)‐pyrene to fraction I consisted of loosely associated radioactivity which is extractable by organic solvents, and of tightly bound (termed “covalently” bound) radioactivity which is not extractable by organic solvents. Increases in the extent of metabolism of benzo(a)pyrene and in the amount of “covalently” bound radioactivity occur with increasing periods of incubation of the cells with the labelled carcinogen. This observation, together with the fact that these increases are dramatically reduced by inhibiting polycyclic aromatic hydrocarbon metabolism (using the inhibitor 7,8‐benzoflavone), suggests that a time‐dependent metabolism of benzo(a)pyrene is required for “covalent” binding to nuclear material. Data are presented suggesting that a two‐step reaction may be involved in the binding of benzo(a)pyrene to subnuclear macromolecules. The fraction I localization of such structurally diverse chemical carcinogens as benzo(a)pyrene and N‐methyl‐N'‐nitro‐N‐nitrosoguanidine suggests that this fraction may localize all species of chemical carcinogens and that this localization may be involved in the chemically induced malignant transformation of cells.
Morphology and pathogenesis of tumors of the thymus and stomach in sprague‐dawley rats following intragastric administration of methyl nitrosourea (MNU)
Authors: Koestner A. W. , Ruecker F. A. , Koestner A.
Published: February 2007

Intragastric intubation of MNU (20 mg/kg twice weekly for 9 weeks) into young Sprague‐Dawley rats resulted in a 100% incidence of thymic lymphomas and gastric carcinomas in animals surviving more than 14 weeks. Progressive thymic atrophy followed the successive MNU administration culminating in marked lymphoid depletion by the 5th week of MNU treatment. At 6 weeks, repopulation of the thymus with lymphoblastic cells was observed, which progressed to thymic neoplasia. The first thymic lymphoma appeared at the 6th week. By the 15th week all rats were either moribund or had succumbed to anoxia caused by pleural effusions associated with thymic neoplasia. Twenty‐six of 31 thymic tumors were classified as lymphocytic lymphomas, 2 as histiocytic, 1 as mixed lymphocytic‐histiocytic, 1 as bimorphic and 1 as an epithelial thymoma. All but 2 lymphomas were restricted to the thymus. Of these 2 (both histiocytic lymphomas), 1 involved the spleen, liver and abdominal lymph nodes and the other infiltrated locally into cervical and thoracic regions. Significant thymic enlargement occurred only after MNU treatment was stopped (MNU acting as an anti‐cancer drug). The gastric carcinomas were restricted to the non‐glandular portion of the stomach and developed as a final step following ulceration, hyperplasia and neoplastic transformation. The short latency period and the high incidence of thymic neoplasms represent valuable criteria for future use of this model for pathomorphogenetic as well as immuno‐and chemotherapeutic investigations.
ADCC effector cells in a murine adenocarcinoma. I. Evidence for blood‐borne bone‐marrow‐derived monocytes
Authors: Haskill J. S.
Published: February 2007

The origin and identity of effector cells for antibody‐dependent cell‐mediated cytotoxicity and/or growth inhibition (ADCC) found in the murine mammary adenocarcinoma T1699 were investigated. Non‐phagocytic, non‐adherent ADCC effector cells were identified in bone marrow, peripheral blood and the host fraction of the tumor but not from lymphoid organs. These cells were shown to be distinct from the specific growth‐inhibitory “armed monocytes” also identified in situ. The ADCC effector cells possess low levels of EA Fc receptors and appear to express a macrophage‐associated antigen. Both the bone‐marrow and the in situ effector cells became phagocytic after overnight incubation, providing further evidence for the monocyte‐macrophage lineage of these cells. The results suggest that bone‐marrow‐derived blood‐borne monocytes are the principal ADCC effector cells localizing in the mammary adenocarcinoma T1699. The parallels between tumor‐induced immunity and cellular resistance to infectious agents involving hypersensitivity reactions and blood‐borne monocytes are discussed.
Incidence of malignant melanoma of the skin in the five nordic countries: significance of solar radiation
Authors: Magnus Knut
Published: February 2007

The incidence of malignant melanoma of the skin has increased rapidly among white people during the last decades. Excellent possibilities for detailed epidemiological analysis of malignant melanoma are provided in the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden), where the five national cancer registries were established during the period 1942–1958. Their materials are based on reports from hospitals and histopathological laboratories and death certificates. The organization of the registries is largely similar, and efforts have been made to bring the materials into conformity. More than 14,000 cases are included in the analysis, which covers the period 1953–1972 in Denmark, Finland and Norway, 1955–1974 in Iceland and 1959–1971 in Sweden. The tumors have been grouped by anatomical site as follows: face, neck/trunk, upper limb, lower limb, and other and unspecified sites. The incidence of malignant melanoma is similar in Denmark, Norway and Sweden. Lower incidence rates are observed in Finland and Iceland. Time trends in incidence are remarkable and clearly statistically significant, except for Iceland where the number of cases was very small. The period for doubling the incidence rate ranged from 10 to 17 years. Striking contrasts by sex are observed when the material is grouped according to primary site. There is a male preponderance for incidence on the neck/trunk and the reverse is found for the lower limbs. There is only a slight increase in incidence of malignant melanoma of the face, whereas for the neck/trunk, particularly among males, and for the lower limbs, particularly among females, there is a consistent upward trend. A difference between the face, on the one hand, and the neck/trunk and lower limbs on the other, is also disclosed in the curves showing the age‐specific incidence rates.

In conclusion, the results indicate that there is a marked real increase in incidence of malignant melanoma of the skin in all the Nordic countries. This increase is in accordance with the hypothesis of the association between solar radiation and risk of cutaneous melanoma, and could possibly be ascribed to changes in habits of leisure and clothing. It ought to be possible to introduce control measures against malignant melanoma which is becoming a serious cancer problem. This is a challenge for future preventive medicine.
Cell mediated immunity during infectious mono‐nucleosis to epstein‐barr virus associated antigens
Authors: Periman Phillip , Levine P. H. , Ablashi D. V. , Royston Ivor
Published: February 2007

Twenty‐three patients with recent infectious mononucleosis were studied for cell‐mediated immunity to Epstein‐Barr virus (EBV)‐associated antigens. By means of a virion‐containing antigen preparation, (P3J), leukocyte migration inhibition was demonstrated in 6 of 13 patients with acute infectious mononucleosis (IM) and in 6 of 10 patients studied during the convalescent period. Inhibition with a soluble antigen (S) preparation was seen in only a few patients at all stages of the illness. Lymphocyte blast transformation on exposure to P3J occurred in 4 of 9 patients with acute IM; no other study group reacted. Control donors lacking anti‐EBV antibodies did not demonstrate migration inhibition or blast transformation with either P3J or S. Control donors with evidence of previous EBV infection did demonstrate migration inhibition with P3J (8 of 12) and S (3 of 10). These studies indicated that cell‐mediated immunity to EBV‐associated antigens could be detected by either leukocyte migration inhibition or lymphocyte blast transformation, but neither assay is diagnostic of infectious mononucleosis.
Mechanism of Corynebacterium parvum anti‐tumour activity. II. Protective effect in T‐cell‐deprived mice
Authors: Mazurek Cypka , Chalvet Huguette , Stiffel Claude , Biozzi Guido
Published: February 2007

The natural resistance to syngeneic mammary carcinoma was reduced by thymectomy alone in adult C3H mice or in mice thymectomized, lethally irradiated and restored with bone‐marrow cells (Tx RB). The protective effect of C. parvum was not modified by adult thymectomy but it was reduced in Tx RB mice. The injection of thymic cells to Tx RB mice or the elimination of T cell precursors in bone‐marrow cells injected in Tx RB mice did not increase the protective effect of C. parvum. These results were compatible with the hypothesis that T cells do not intervene in the mechanism of C. parvum protective effect.
Production of hybrid cells by fusion of human malignant tumour cells and primary mouse embryo cells
Authors: Watkins J. F.
Published: February 2007

Hybrid cells with a subtetraploid mouse chromosome complement were produced by fusion of three types of human tumour cells with primary mouse embryo cells. The most frequently present presumptive human chromosome was 21. Numerous chromosome rearrangements were present. Some hybrid cells produced regressing tumours in mice.
Bovine leukemia virus specific antibodies among french cattle. II. Radioimmunoassay with the major structural protein (BLV P24)
Authors: Levy D. , Deshayes L. , Parodi A. L. , Levy J. P. , Stephenson J. R. , Devare S. G. , Gilden R. V.
Published: February 2007

A radioimmunoassay (RIA) for the major internal protein of the bovine leukemia virus (BLV p24) was established using anti‐BLV p24 natural antibodies and purified 125I‐labelled BLV p24. The final precipitation of the immune complexes was realized by a preparation of inactivated Stophylococcus aureus Cowan I. Sera from 363 cows belonging to (1) leukemic herds, (2) non‐leukemic but BLV‐exposed herds, and (3) apparently unexposed herds were studied comparatively in BLV p24 RIA, complement fixation and immunodiffusion. The BLV p24 RIA appeared much more sensitive than the two other methods in the detection of positive sera. With this method 100% of the leukemic animals, excluding those with juvenile lympho‐sarcoma, presented very high antibody titers (±10,000). Practically all cows with persistent lymphocytosis were also positive with slightly lower levels of antibodies, confirming the relationship between BLV infection and the persistent lymphocytosis. Moreover, about two‐thirds of the hematologically suspect animals and one‐third of the normal animals from BLV‐exposed herds were found positive, whereas 100% of the sera from unexposed cows remained negative for anti‐BLV p24 antibodies.
Interspecies‐, species‐ and type‐specific T antigenic determinants of human papovaviruses (JC and BK) and of simian virus 40
Authors: Beth E. , Cikes M. , Schloen L. , di Mayorca G. , Giraldo G.
Published: February 2007

Immunofluorescence tests, absorption studies and quantitative analysis by a very sensitive 51Cr micro‐complement fixation (CF) technique were used to define the degree of relatedness between the tumor (T) antigens induced by human papovaviruses, strain JC and BK, with simian virus 40 (SV40) and mouse polyoma virus (PyV). Antisera against JCV, BKV, SV40 and PyV T were raised in tumor‐bearing hamsters. The data obtained indicate that T antigens of JCV, BKV and SV40 possess various subspecificities which can be distinguished and looked upon as interspecies‐, species‐ and type‐specific antigenic determinants. It was found that JCV T and BKV T synthesized in transformed hamster cells share about the same amount (20%) of interspecies cross‐reacting antigen with SV40 T from H‐50 cell extracts (transformed hamster cells). Although hamster cells transformed by PyV showed definite PyV T reactivity, no cross‐reactivity, at least with the sera used, was found with human papovavirus and SV40 T antigens. Furthermore, degree of heterogeneity was observed within the T antigen complex derived from different SV40‐transformed cells.
Two‐step chromosomal control of tumorigenicity of chinese hamster cells in nude mice
Authors: Ebina T. , Koi M. , Ishida N.
Published: February 2007

A simple method for microinjecting isolated chromosomes into a single living cell under an inverted microscope has been developed. Of the 368 injected cells, 85 were able to form a colony and could be cloned. Clones of Chinese hamster V79 cells microinjected with chromosomes isolated from murine D56 cells [V79 (D56) cells] were tested for tumorigenicity in immunodeficient nude mice and for colony‐forming ability in soft agar.

Untreated recipient V79 cells were highly tumorigenic and had a high colony‐forming ability in soft agar. In contrast, two out of the 21 microinjected clones tested were non‐tumorigenic in nude mice and had only weak colony‐forming ability in soft agar.

The chromosome banding pattern was analyzed in microinjected clones and tumors derived from cells of these clones. In cells of the two non‐tumorigenic clones, a telocentric chromosome 1 (t1) was specifically involved in translocations with other chromosomes or chromosome fragments. In all tumor cells obtained from nude mice, a supernumerary piece or a whole biarmed chromosome 14 (b14) was specifically found. The results suggest that the t1 chromosome bears the gene which controls in vitro transformation and that the additional genetic change, i.e. the extra piece of b14 chromosome, was required for tumor formation in vivo.
Analysis of established human carcinoma cell lines for lymphoreticular‐associated membrane receptors
Authors: Kerbel R. S. , Pross H. F. , Leibovitz A.
Published: February 2007

Thirty‐one different long‐term established human carcinoma culture cell lines were examined for the presence or absence of receptors for the Fc portion of immunoglobulin G (IgG) (“Fc receptors”), the third component of complement (C3 receptors), sheep erythrocytes and mouse erythrocytes. Included in the catalogue of lines tested were adeno‐carcinoma of the adrenal cortex, colon, rectum, lung, liver, breast and kidney, and carcinomas of the uterine cervix, bladder and vulva. All lines were found to be consistently Fc receptor‐negative, as assayed by rosette formation with sheep erythrocytes coated with subhemagglutinating amounts of anti‐sheep erythrocyte antibodies, or bovine erythrocytes heavily coated with non‐hemagglutinating anti‐bovine erythrocyte antibodies. This is similar to results obtained with murine tumors: carcinomas are consistently Fc receptor‐negative, while those lines which are Fc receptor‐positive are invariably lymphoreticular in nature. The human carcinoma cell lines were also negative for complement (C3) receptors and spontaneous T and B rosette markers. It is proposed that, in most cases, rosette‐forming cells found in primary human carcinomas are, as in the mouse or rat, representative of infiltrating non‐malignant lympho‐reticular cells.
Complement‐dependent cytotoxic antibodies in the course of cervical carcinoma
Authors: Christenson Brith
Published: February 2007

Complement‐dependent cytotoxic antibodies to three cervical carcinoma cell lines (Me‐180, SW‐732 and HeLa) and to Herpes simplex virus type 2 (HSV‐2)‐infected cells were determined in a long‐term study of women with cervical carcinoma. Cytolysis of surface antigens differed significantly between the cervical carcinoma cell lines and HSV‐2. Regression of the tumor during treatment was accompanied by decreasing cytolysis in the cervical carcinoma lines, while tumor bearers and patients who became severely ill had high or increasing cytotoxic antibodies. The opposite was noted for the antibody response to HSV‐2 infected cells: patients with less advanced cancer had significantly higher cytolytic activity than those who were severely ill or had advanced cancer; long‐term survivors demonstrated high, stable lysis of HSV‐2 infected cells. As a control of the cervical carci noma cell lines, cytolytic activity was tested also on a lung carcinoma cell line, A‐549. No significant differences were found between the patients with cervical cancer and the control women. Tumor bearers and patients treated for advanced cervical cancer showed a slight but non‐significant increase in cytolytic activity on the A‐549 line.
Surface glycoprotein patterns of normal and malignant human lymphoid cells. I. T cells, T blasts and leukemic T cell lines
Authors: Andersson Leif C. , Gahmberg Carl G. , Nilsson Kenneth , Wigzell Hans
Published: February 2007

Exposed surface glycoproteins of resting and in vitro activated human T lymphocytes and leukemic T‐cell lines were labelled by the galactose oxidase‐tritiated sodium borohydride method. The labelled glycoproteins were separated by polyacrylamide slab gel electrophoresis and visualized by auto‐radiography. The basic glycoprotein patterns of the T lymphocytes and T blasts were found also in the leukemic T cells. The glycoprotein pattern of the T‐cell lines was easily distinguishable from that of other hematopoietic cell lines. The findings suggest that: (1) surface glycoprotein analysis might be useful for the identification of cell lines and for the differential diagnosis of hematopoietic malignancies; and (2) cells of cultured T lines may be used for the identification and preparation of T lymphoid differentiation antigens and perhaps also tumor‐associated surface molecules.
Lymphocyte subpopulations and mitogenic responses in nasopharyngeal carcinoma, prior to and after radiotherapy
Authors: Lamelin J.‐P. , Ellouz R. , De‐Thé G. , Revillard J. P.
Published: February 2007

Eighteen patients with nasopharyngeal carcinoma (NPC) were compared to matched controls, before or after cobalt therapy, for the ability of their peripheral blood lymphocytes to: (1) form E and EAC rosettes and (2) mount a proliferative response with PHA, Con A and ALG. A slight decrease in the percentage of E rosettes and a moderate hyporesponsiveness to PHA and Con A were observed before treatment. The statistical significance of these alterations was borderline. Within the group of treated patients a much greater depression, including the response to ALG, was found, although a few long‐term survivors responded to mitogens as well as the controls. These findings stress the difficulty of interpreting the results of a longitudinal study of cell‐mediated immunity, specific or non‐specific, in cancer patients. Finally, by comparing the proHferative response to the three mitogens before and after radiotherapy, it is suggested that their differential effect on these responses might be used in man, as it was in mice, to delineate lymphocyte subpopulations.
Avian retrovirus‐induced surface antigens and their cross‐reactivity with chemically‐transformed cells and primary embryonic cells of Japanese quails
Authors: Hayami Masanori , Ignjatovic Jagodina , Bauer Heinz
Published: February 2007

By testing spleen cells from avian leukosis (ALV) and avian sarcoma virus (ASV)‐injected Japanese quails in a microcytotoxicity assay against various target cells, we have demonstrated the existence of several target antigens. With non‐transformed ALV‐infected Japanese quail cells used as target cells, an avian retrovirus subgroup‐specific destruction was obtained when spleen cells from animals infected with either avaian sarcoma or leukosis virus of the same subgroup were employed. This reaction is probably due to the virus envelope glycoproteins (Ve‐gp) expressed on the cell surface. Apart from this subgroup‐specific reaction, avian retrovirus group‐specific destruction of ASV‐trans‐formed cells was demonstrated by means of effector cells immunized with ASV of a different subgroup. This reaction is restricted to transformed cells and not due to the virus envelope glycoprotein because the same effector cells are not cytotoxic to ALV‐infected non‐transformed cells but cytotoxic to sarcoma‐virus‐transformed cells which lack Ve‐gp. Quail methylcholanthrene‐tumor cells which show a transformation phenotype similar to that of ASV‐transformed cells but which are free of detectable endogenous and exogenous retrovirus were also destroyed by the spleen cells from ASV tumor bearing animals. The same effector cells also exerted a weak cytotoxic effect on uninfected primary embryo cells but not to embryo cells after several passages.
Immunity to MCA‐induced rat sarcomas: Analysis of in vivo and in vitro results
Authors: Harmon Richard C. , Clark Edward A. , Reddy A. Lakshma , Hildemann William H. , Mullen Yoko
Published: February 2007

Three in vivo techniques were used to establish the specificity of tumor immunity induced after sensitization of F344 rats to syngeneic MCA‐induced sarcomas: (1) post‐excision resistance to tumor challenge, (2) passive tumor neutralization (the Winn test), and (3) concomitant immunity. In general, these assays revealed unique non‐crossreactive antigens associated with each of three sarcomas, FMF1, FMM2, and FMM3. However, spleen cells from tumor‐sensitized rats did not demonstrate cell‐mediated cytotoxicity in vitro corresponding to the specificity of tumor resistance in vivo. In the (3H)‐proline cytotoxicity assay, spleen cells from FMM3 tumor‐bearing rats or from FMM3 tumor‐immune rats were not selectively cytotoxic for cultured FMM3 target cells. Parallel analysis of spleen cells from normal or FMM3‐sensitized rats using the Winn assay and the (3H)‐proline assay revealed that (1) spleen cell cytotoxicity in vitro did not correlate with effective tumor protection in vivo; and (2) normal spleen cells were cytotoxic against cultured sarcoma target cells in vitro and inhibited tumor growth in vivo. Thus, passive tumor protection by normal spleen cells in vivo corresponded with the demonstration of natural cytotoxicity in vitro, but induced specific anti‐tumor reactivity was observed only in vivo.
Analysis of karyotype variation following carcinogen treatment of chinese hamster primary cell lines
Authors: Connell J. R. , Ockey C. H.
Published: February 2007

Chinese hamster primary fibroblasts derived from several embryos were treated with the carcinogens benzo(a)pyrene, 7,12‐dimethylbenz(a)anthracene or N‐methyl‐N'‐nitro‐N‐nitrosoguanidine. Karyotype analysis, sister chromatid exchange frequency, evidence of transformation by growth in agar, cell morphology and reaction to cytocholasin B were tested at regular intervals over many culture passages. Carcinogen treatment was found to shorten the time period before onset of permanent karyotypically changed stem and side lines and in vitro transformation. Chromosomes X, 6 and 10 were more frequently involved in all cultures in these karyotype changes which were usually preceded by a period of chromosome variation. Spontaneous chromatid aberrations and aneuploidy increased in frequency with time in culture and generally appeared prior to the expression of transformation. No specific chromosomes were involved with the different carcinogens. There was no correlation between in vitro transformation and karyotype evolution and the criteria for transformation were present independently of one another. It is suggested that the lack of correlation between the parameters tested indicates that the expression of in vitro transformation is a result of selection for growth advantage from a cell population expressing an increasing degree of genetic instability and variation with time in culture.
Virus expression in different tissues of normal and tumor‐bearing mice inoculated with a murine leukemia virus
Authors: Youn J. K. , Santillana M. , Hue G. , Barski G.
Published: February 2007

Evolution of virus expression in different lymphoid organs as well as in solid syngeneic tumors of mice inoculated with an MuLV was studied with the aid of in vitro XC co‐culture technique. When normal adult mice of strain XLII were inoculated intraperitoneally with a cultured Rauscher virus (RC), the virus could be detected, 10 days after inoculation, only in bone marrow in small amounts and there‐after no virus could be found in any of the organs tested, including bone marrow, spleen, thymus, lymph node and kidney. However, when age‐ and sex‐matched parallel mice bearing syngeneic subcutaneous non‐viral tumors were inoculated similarly with the RC virus, the virus could be detected abundantly not only in bone marrow and spleen but also in tumors during the first 3 weeks and even 6 weeks after virus inoculation. Transitional decrease or disappearance of the virus was observed around the 25th‐31st day in organs and tumors of the inoculated mice. When the tumor mass was removed from these mice by surgery, the virus disappeared rapidly and definitely from all the organs tested. The virus recovered from in vitro explanted and cultured tumors, taken from mice inoculated with the virus, induced typical lymphoid leukemia in BALB/c mice inoculated as newborns. However, from certain aspects (hypertrophy of the thymus and lymph nodes), this virus was different from the original RC virus.
Increase in immunogenicity of a pulmonary squamous‐cell carcinoma, propagated in vitro
Authors: Jamasbi Roudabeh J , Nettesheim Paul
Published: February 2007

The chemically induced, non‐immunogenic lung squamous‐cell carcinoma (MSC‐10) propagated in vitro gradually loses tumorigenicity in immuno‐competent hosts with increasing in vitro passage. This was found to be related to an increase in antigenicity, since immunosuppressed hosts (thymectomy plus 600 rads whole body X‐irradiation) supported the growth of tumor cells, whereas immunocompetent recipients did not. The antigens involved in rejection are not heterologous serum proteins present in culture media since the cell line grown in isologous serum is also rejected. Immunization with the in vitro tumor line partially protected against the parental in vivo line, therefore the antigens involved must be present on both tumor lines. Inoculation of the cultured cell line into normal or immunosuppressed hosts produced tumors with the same histological characteristics as those of the in vivo tumor line. We concluded that by in vitro culture the weakly antigenic carcinoma becomes more immunogenic and thereby capable of inducing transplantation resistance. The cultured tumor cells retain their antigenic specificity and histologic characteristics while increasing their antigenic potency.
Mechanism of the establishment of epstein‐barr virus genome‐containing lymphoid cell lines from infectious mononucleosis patients: Studies with phosphonoacetate
Authors: Rickinson A. B. , Finerty S. , Epstein M. A.
Published: February 2007

A concentration of disodium phosphonoacetate (PA) has been defined which will reduce the synthesis of infectious EB virus in a producer cell line to 1% of control values but which will not affect the growth of EB virus‐transformed cells in a 12‐week colony‐forming assay. When total mononuclear cells or T‐lymphocyte‐depleted mononuclear cells from the blood of acute IM patients were cultured in the presence of PA at the above concentration, the regular establishment of EB virus genome‐containing cell lines seen in control cultures was almost totally abolished. In further experiments, when T‐lymphocyte‐depleted IM mononuclear cells were co‐cultivated with foetal cells of the opposite sex in the presence and absence of PA, cell lines of mixed or of exclusively foetal origin were obtained not only from control co‐cultures but also on those rare occasions when transformed foci developed in PA‐treated co‐cultures. The results suggest that all cell lines derived from the blood of IM patients are initiated in culture by a two‐step process of virus release and secondary infection, and argue against the occurrence of any direct outgrowth of IM cells transformed by the virus in vivo.
Growth requirements of human mammary epithelial cells in culture
Authors: Taylor‐Papadimitriou J. , Shearer M. , Stoker M. G. P.
Published: February 2007

Colony‐forming epithelial cells can be separated from the non‐dividing “foam cells” in human milk by differential adhesion to glass and freezing. The growth of such partially purified mammary epithelial cells is stimulated by co‐culture with non‐dividing feeder cells. Foam cells, mitomycin‐treated mouse fibroblast lines and human mammary fibroblasts and calf lens epithelial cells are all effective in promoting mammary epithelial cell growth. Contact between epithelial cells and feeders is not required for the growth‐promoting effect. The mitogenic effect of epidermal growth factor on mammary epithelial cells also requires feeder cell activity.
Immunostimulation of chemical oncogenesis in the mouse
Authors: Prehn Richmond T.
Published: February 2007

Past work has demonstrated, both in vivo and in vitro, that a weak immune reaction can stimulate rather than inhibit the growth of many transplantable tumors. It was therefore predicted that animals with a weak immunological capacity would be more susceptible to tumor induction than would those with either a minimal or a maximal capacity. X‐rayed, thymectomized mice were inoculated with various numbers of normal syngeneic spleen cells and were subsequently exposed to various degrees of oncogenic stimulus by 3‐methylchol‐anthrene in the form of subcutaneous wafers. As expected, it was found that among animals exposed to a high oncogenic stimulus, the sarcoma incidence was significantly higher among those animals that had received small numbers (104) of spleen cells than among those that had either received none (0) or the maximal number (107). In contrast, when the oncogenic stimulus was low, the tumor incidence was the same in all groups regardless of the numbers of spleen cells the animals had received. Since the average immunogenicity of sarcomas has been shown to be directly related to the concentration of the chemical oncogen and inversely to the tumor latency, it can be inferred that the higher tumor incidence associated with 104 spleen cells in the experiments with a high oncogenic stimulus probably depended upon the immunogenicities of the induced tumors and was therefore consistent with an immunostimulation of oncogenesis.
Detection of a nuclear, EBNA‐type antigen in apparently EBNA‐negative Herpesvirus papio (HVP)‐transformed lymphoid lines by the acid‐fixed nuclear binding technique
Authors: Ohno Shinsuke , Luka Janos , Falk Larry , Klein George
Published: February 2007

In agreement with the findings of previous authors, we could not detect a virally determined nuclear antigen in Herpesvirus papio (HVP)‐transformed baboon lymphoid lines by anticomplementary staining in situ, as for EBNA. However, by means of our recently developed acid‐fixed nuclear binding technique an EBNA‐like antigen could be readily demonstrated, after extraction from both producer and non‐producer lines. We propose to designate the antigen as HUPNA. It can be detected by a human anti‐EBNA antibody, suggesting cross‐reactivity, if not identity, between EBNA and HUPNA. HVP‐DNA carrying non‐producer lines, negative for in situ ACIF stainability but capable of yielding HUPNA by the nuclear binding technique, can be superinfected with EBV, with brilliant EBNA expression as the result, suggesting that the defective in situ staining is a property associated with the baboon HVP, rather than the baboon lymphoid cell per se.
The effect of chronic protozoan infection by Babesia rodhaini on leukemogenesis in mice
Authors: Hugoson G. , Lagerlöf B. , Thorell B.
Published: February 2007

The effect of chronic infection with the protozoan parasite Babesia rodhaini on the subsequent development of mouse leukemia was investigated in three different murine leukemia‐lymphoma model systems: congenital lymphoma (in AKR mice), irradiation‐induced lymphoma (in C57BL mice), and Rauscher‐virus‐induced leukemia in NMRI mice. Leukemia incidence was significantly greater than in controls in Babesia‐infected (NMRI strain) mice that had been infected with an adjusted dose of Rauscher leukemia virus.
Screening of human brain tumors for SV40‐related T antigen
Authors: Tabuchi Kazuo , Kirsch Wolff M. , Low Margaret , Gaskin Doris , van Buskirk John , Maa Shane
Published: February 2007

A series of 39 human brain tumors has been screened for the presence or absence of SV40‐related T antigen by the direct and indirect immuno‐peroxidase methods. Two tumors of ependymal origin (malignant ependymoma, choroid plexus papilloma) revealed markedly positive nuclear staining for T antigen both in vivo and in vitro. The relationship of these tumors to their experimental counterparts inducible by recent human papova‐virus isolates is discussed.
Chemical transformation of human revertant cells induced by murine sarcoma virus
Authors: Cho Han Y. , Arnstein Paul , Rhim Johng S.
Published: February 2007

A human revertant cell line, derived from non‐producer human osteosarcoma cells (NP/KHOS) induced by Kirsten murine sarcoma virus, was treated in vitro with various levels of polycyclic aromatic hydrocarbons (3‐methylcholanthrene, 7,12‐dimethylbenz(a)anthracene, and benzo(a)pyrene [BP] or dimethyl sulfoxide (control). Cells treated only with 3‐methylcholanthrene and 7,12‐dimethyl‐benz(a)anthracene underwent morphological alteration in vitro, and produced tumors when injected into NIH nude mice. These human revertant cells may be a useful in vitro tool in screening for the potentital chemical carcinogens in human cell systems.
Characterization of the human natural killer (NK) cell in blood and lymphoid organs
Authors: Eremin O. , Coombs R. R. A. , Plumb D. , Ashby J.
Published: February 2007

The human natural killer (NK) cell in peripheral blood is a non‐thymus‐dependent, (Fc+ C3−), Ig‐bearing lymphocyte and is probably identical to the human K cell, although not requiring the Fc receptor, in contrast to the K cell, for the lytic process. The human NK cell in tonsil and lymph node, on the other hand, is a non‐Ig‐ bearing T lymphocyte, lacking both Fc and C3 receptors.
Immunotherapy of murine leukemia. I. protection against friend leukemia virus‐induced disease by passive serum therapy
Authors: Collins Jeffrey J. , Sanfilippo Fred , Tsong‐Chou Lynn , Ishizaki Ryo , Metzgar Richard S.
Published: February 2007

Passive serum therapy with chimpanzee anti‐serum raised against Friend leukemia virus (FLV) or the major viral envelope glycoprotein of FLV, gp71, has been shown to be effective in protecting mice against the development of virus‐induced disease. The heterologous serum was administered in four doses beginning 3 days after virus inoculation and the mice were followed for the development of splenomegaly, virus level, and the induction of a host anti‐viral immune response. The latter was measured by an in vitro humoral cytotoxicity assay using FLV‐releasing mouse cells as targets, as well as by direct radioimmunoassay for the presence of mouse antibodies capable of binding FLV gp71. The results indicate a close correlation between the development of anti‐viral humoral immunity and protection against splenomegaly, with both of these parameters being inversely related to serum and spleen infectious virus titers. Recognition of and response to the administered heterologous immunoglobulin in by the recipient animal does not appear to represent an integral part of the mechanism leading to protection, as determined by the absence of mouse antibodies capable of binding chimpanzee γ‐globulin, as well as by the equal efficacy of the passive serum transfer protocol in mice after induction of tolerance to chimpanzee γ‐globulin. It is suggested that passive serum therapy protection may function via a mechanism involving the reduction of the virus burden below a level which is immunosuppressive, allowing the development of a host anti‐viral immune response which is necessary for elimination of virus and/or infected cells leading to long‐term resistance.
Inhibition and promotion of tumor growth by BCG: Evidence for stimulation of humoral enhancing factors by BCG
Authors: Ishibashi Tsuneo , Yamada Hozumi , Harada Susumu , Harada Yasuko , Takamoto Masahiro , Sugiyama Kotaro
Published: February 2007

Effects of pretreatment with BCG, strain Japan, on tumor growth were studied using a transplantable methylcholanthrene (MCA)‐induced fibro‐sarcoma in C3H/He mice. Injection of BCG 7 weeks before tumor inoculation at a site distant from the tumor caused a slight inhibition of tumor growth. A low dose of tumor cells did not grow at the BCG‐primed site when BCG was injected 7 and 11 weeks before the tumor. When a high dose was inoculated into the BCG‐primed site, inhibition of the primary tumor occurred in mice which had received BCG 7 weeks previously, but the number of distant metastases in the popliteal lymph node and the lungs was increased in mice pretreated with BCG at any time. Furthermore, post treatment with BCG at a site distant from the tumor caused promotion of tumor growth. Enhanced antibody formation and suppression of delayed type hypersensitivity(DTH) occurred in tumor‐bearing mice. BCG treatment of such mice caused a vigorously enhanced antibody formation and a marked suppression of DTH. The sera from tumor‐bearing mice enhanced tumor growth. Tumor growth was suppressed in splenectomized mice. These findings suggested that antibodies against tumor‐specific antigens enhanced tumor growth in this system and that BCG treatment of tumor‐bearing mice stimulated formation of antibodies probably acting as blocking factors.
In vitro and in vivo expression of original and foreign H‐2 antigens and of the tumor‐associated transplantation antigen of a murine fibrosarcoma
Authors: Carbone Giusi , Invernizzi Giovanni , Meschini Angela , Parmiani Giorgio
Published: February 2007

We have previously shown that the methyl‐cholanthrene‐induced BALB/c fibrosarcoma C‐1 syngeneically transplanted in vivo expressed, in addition to its original H‐2d and tumor‐associated transplantation antigens, also the foreign H‐2Kk 23, 1, 5, 11, 25 specificities. In the present study we have investigated the expression and the immunogenicity of these antigens on an in vitro line of C‐1 tumor. The binding of C57BL/6J or C3Hf anti‐BALB/c sera or that of monospecific alloantisera to H‐2d specificities on plated C‐1 cells (evaluated by the indirect isotopic 125I‐antiglobulin assay) showed that the expression of H‐2d antigens was very low or undetectable on the tumor kept in vitro. Absorption by the in vivo and in vitro maintained C‐1 cells of the complement‐dependent cytotoxicity on BALB/c normal lymphoid cells of the C75BL/6J anti‐BALB/c serum confirmed the lower expression of H‐2d antigens on C‐1 kept in vitro as compared to the in vivo transplanted tumor. The H‐2k antigens found on C‐1 were also examined by the above methods using BALB/c anti‐C3Hf, anti‐AKR, anti‐C57BL/6J polyspecific sera and also monospecific alloantisera directed to H‐2k antigens. The C‐1 cultured cells displayed a significant reduction of H‐2k antigens as compared to the in vivo C‐1 tumor, the antigen 5 being undetectable on the in vitro cells. Allogeneic and syngeneic sera raised against in vitro or in vivo C‐1 cells were tested on either BALB/c or C3Hf normal lymph‐node cells by the complement‐dependent cytotoxicity assay. A significantly higher titer of cytotoxic antibodies to H‐2d and to H‐2k was obtained in the allogeneic and syngeneic sera respectively, after immunization with the in vivo C‐1 cells as compared to sera raised against the in vitro tumor line. Transplantation studies showed that both in vitro and in vivo C‐1 lines possess the same tumor‐associated transplantation antigen whose expression was non‐significantly reduced on the cultured cells.
Establishment of marek's disease lymphoblastoid cell lines from transplantable versus primary lymphomas
Authors: Calnek B. W. , Murthy K. K. , Schat K. A.
Published: February 2007

Six new Marek's disease (MD) lymphoblastoid cell lines were established in vitro by cultivation in medium containing 2‐mercaptoethanol (2‐ME). Attempts using primary lymphoma cells were generally unsuccessful; only one of 28 lymphomas yielded a cell line and that one came from an experimentally immunosuppressed chicken. In contrast, two of seven low‐passage, and two of two established MD transplantable lymphomas grew readily in vitro. A sixth line was obtained using buffy coat cells from leukemic chicken. It was concluded that the use of transplantable tumor cells and a medium containing 2‐ME provided a combination highly sulted to the establishment of cell lines from MD.
Characteristics of hamster cells transformed by the combined action of chemical and virus
Authors: Hatch George G. , Balwierz Patrick J. , Casto Bruce C. , Dipaolo Joseph A.
Published: February 2007

Pretreatment of hamster cells with chemical carcinogen enhances transformation by a simian adenovirus, SA7. Such transformants were compared to cells transformed by SA7 alone for the presence of virus‐specified antigens, and for the ability to clone in soft agar and to form progressively growing sarcomas in hamsters. The SA7 “T” antigen content and the relative cloning efficiencies in agar of cell lines of both groups were similar. Some cell lines obtained by pretreatment with chemical carcinogen, however, produced a higher incidence of tumors, suggesting that the chemical carcinogen was involved in the transformation of cells by virus. A further indication that these cells differed from cells transformed by virus alone was obtained with MCA‐transformed fibroblast cell lines that were subsequently also transformed in vitro by SA7 to cuboidal (SA7 type) morphology. These MCA‐SA7‐transformed cells produced a higher incidence of sarcomas than cells transformed by virus alone, but a lower tumor incidence than the parental MCA line.
Induction of ebna precedes the first cellular S‐phase after ebv‐infection of human lymphocytes
Authors: Einhorn Lena , Ernberg Ingemar
Published: February 2007

Using a combination of immunofluorescence and autoradiography, we studied the appearance of EBNA and DNA synthesis in cord‐blood lymphocytes after infection with EBV derived from the B95‐8 cell line. EBNA appeared between 12 and 25 h after addition of the virus. DNA synthesis was detected in EBNA‐positive cells approximately 20 h after the appearance of EBNA. This shows that EBNA induction precedes the first cellular S‐phase and suggests that the cells have not yet entered the cell‐division cycle when EBNA appears. Little, if any, of the total DNA synthesis induced at this stage can be attributed to EBV‐mediated immunologic stimulation.