bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of correlation between in vivo and in vitro assays for the detection of virus released from clones of friend erythroleukemia cells
Authors: Bertolini Luisa , Revoltella Roberto , Bendinelli Mauro , Friend Charlotte
Published: February 2007

The biological properties of the virus synthesized by 18 clones of a line of mouse bone‐marrow hematopoietic cells transformed in vitro by the polycythemic strain of Friend leukemia virus (FLV‐P) were compared. In vitro assays were performed to determine whether the virus released into the culture fluids was ecotropic or xenotropic, and in vivo assays were carried out to determine spleen focus formation and leukemogenicity in susceptible DBA/2J and BALB/c mice. A number of clones released virus which reproduced the entire range of effects typical of the FLV‐P complex. However, in other clones, there appeared to be no correlation between the assays for leukemogenicity and the assays for either ecotropic virus, reverse transcriptase activity, or virus antigens. Xenotropic virus was not detected in any of the cultures. These results suggest that the FLV‐P complex contains a heterogeneous population of viruses, but the possibility that the differences observed may be due to the inability of FLV‐P to be expressed fully in some clones cannot be excluded.
Metabolic inhibitors render ‘resistant’ target cells sensitive to natural killer cell‐mediated lysis
Authors: Kunkel Lori A. , Welsh Raymond M.
Published: February 2007

L‐929 cells were lysed by activated but not by endogenous natural killer (NK) cells, as reported previously. Nevertheless, L‐929 cells bound to endogenous NK cells, as shown by target binding cell, cold target competition, and monolayer absorption assays. Treatment of L‐929 cells with actinomycin‐D or cycloheximide rendered them sensitive to lysis by endogenous NK cells and markedly increased their sensitivity to lysis by activated NK cells. Treatment with these drugs under the prescribed conditions did not affect the binding of L‐929 cells to NK cells. Since others have shown that treatment with these drugs inhibits membrane repair processes and renders cells more sensitive to complement‐mediated lysis, we hypothesize that membrane repair may be an important factor influencing a cell sensitivity to NK cells. This may be more important than NK‐binding ability, since most cells can be lysed by (and therefore bind to) activated NK cells.
Induction of a malignant lymphoreticular cell line which displays spontaneous killer‐cell activity
Authors: Kerbel R. S. , Roder C. , Pross H. F.
Published: February 2007

The origin and properties of a new malignant „spontaneous killer”︁ cell line are described. The tumor, known as M9‐78, was produced by treatment of tissue cultures consisting mostly of dividing DBA/2 mouse macrophages with the chemical carcinogen, 3‐methyl‐cholanthrene. Logarithmic phase cultures were treated for 6 days followed by further culture for 1 month in the absence of carcinogen. Subcutaneous injection of normal DBA/2 mice with 2.0 × 105 cells led to the formation of palpable tumors at the site of inoculation within 14 days; the tumors grew progressively and were highly metastatic. The malignant cells, though Fc‐receptor‐positive, did not possess many other properties normally associated with macrophages; morphologically, they bore a strong resemblance to bone‐marrow‐derived promonocytes. Because promonocytes have been shown previously to possess both antibody‐dependent killer (K) cell as well as antibody‐independent spontaneous killer‐cell function, the M9‐78 cells were tested for these biologic activities. The following results were obtained: (1) adherent, but not non‐adherent, M9‐78 tissue culture cells spontaneously killed a wide variety of (though not all) tumor‐cell‐line targets in long‐term (18‐24 h) 51Cr release, whereas no killing was seen in short (4 h) assays; (2) the cells were not capable of killing nucleated targets by antibody‐dependent cell‐mediated cytotoxicity; (3) a number of clones were obtained and tested for spontaneous killer‐cell activity: some were highly active, whereas others were negative, with different patterns of specificity being evident; (4) the clones were unstable; (5) the pattern of target killing, when compared to normal spleen control NK cells, suggested the M9‐78 cells were similar to activated macrophages or promonocytes in their target selectivity, although no definitive evidence was obtained which could implicate a promonocyte or monocyte origin for the cells.
Mutants of adenovirus type 12 after adaptation to growth in tumor cell lines. II. Reproducible acquisition of additional sequences after adaptation to a human cervical cancer line
Authors: Kruczek Ingeborg , Schwarz Elisabeth , Hausen Harald Zur
Published: February 2007

Adaptation of adenovirus type 12 to growth in a human cervical cancer line (C4/1) results in the reproducible selection of viral mutants carrying additional DNA sequences at the right‐hand end of the genome which range in size from 190 to 400 base pairs. The viral mutants have selective growth advantage in comparison to the non‐affected wild type, even after subsequent passages in human KB cells, commonly used for adenovirus propagation. Detailed restriction endonuclease analysis of one of the mutant DNAs shows that the additional sequences are located within the terminal 195 base pairs of the right end of the genome.
Sister chromatid exchange and growth kinetics in untreated acute leukemia
Authors: Becher Reinhard , Zimmer Gabriele , Schmidt Carl G.
Published: February 2007

Sister chromatid exchange (SCE) frequency has been analysed after short‐term culture of leukemic bone marrow cells of eight untreated patients with acute leukemia. Compared to normal bone marrow, results show a statistically significant decrease of SCE (p < 0.001) in euploid as well as in aneuploid leukemias, ranging from 2.11 to 2.97 SCE per metaphase. The different SCE values were not related to contraction status of chromosomes and could not be explained by the age of patients. Therefore, low SCE may be a typical feature of leukemic cells. An examination of growth rates by the SCE technique revealed a high turnover of normal bone marrow cells. About 80% of the cells did not need more than 50 h to run two or three cell cycles. Leukemic cells, however, apparently divided more slowly, which is in good agreement with data obtained by autoradiographic methods.
Antibody‐induced augmentation of murine natural killer cell activity
Authors: Brunda Michael J. , Herberman Ronald B. , Holden Howard T.
Published: February 2007

Antibodies reactive with effector cells were shown to augment the cytotoxicity of spleen cells from athymic nude and euthymic mice. The addition of alloantibody to the assay or pretreatment of the effector cells with alloantibody resulted in increased cytotoxicity against the human cell K562, a relatively poor target for spontaneous mouse NK activity. When monoclonal antibodies were tested, cytotoxicity was markedly increased by some antibodies, such as anti‐H‐2, anti‐la, and anti‐Thy 1.2, while others had no effect. The degree of augmentation of cytotoxicity was dependent on the concentration of antibody added. Nylon‐wool‐nonadherent nu/nu splenic effector cells mediated the antibody‐induced cytotoxicity and anti‐asialo GMI plus complement abolished activity, indicating that the cells mediating the cytotoxicity were NK cells and not mature T cells, B cells or macrophages. When spleen cells from mice having different levels of NK activity were evaluated in this system, the magnitude of augmentation by antibody correlated with the level of spontaneous NK activity and no increased cytotoxicity was found with cell populations that had low spontaneous NK activity. Testing a panel of target cells, showed that certain human and mouse cell lines, with low to moderate susceptibility to spontaneous NK activity, were sensitive to antibody‐induced NK‐cell‐mediated cytotoxicity whereas others were completely resistant. Both Fc‐IgG receptor‐positive and ‐negative cell lines were susceptible target cells. These results indicate that antibodies reactive with murine NK cells can increase their cytolytic activity.
Tumor neutralization by immune in vitro‐sensitized splenocytes depends on an interaction with bone‐marrow‐derived cells
Authors: Scuderi Philip , Rosse Cornelius
Published: February 2007

In a Winn assay, the inhibition of methylcholanthrene‐induced sarcoma growth by tumor‐immune, secondarily in vitro‐sensitized splenocytes was augmented by normal unsensitized bone‐marrow cells. Bone‐marrow cells augmented the effect of a fixed number of sensitized splenocytes in a dose‐dependent manner, yet had no tumor‐neutralizing capacity by themselves. The marrow's capacity to enhance tumor neutralization was not shared by normal splenocytes, thymocytes or lymph‐node cells. When two non‐cross‐reacting tumors were used, marrow cells were capable of augmenting tumor neutralization only if admixed with sensitized splenocytes and the sensitizing neoplasm. Equal numbers of bone‐marrow cells administered intravenously to recipients of an admixture of sensitized splenocytes and tumor were unable to augment neutralization, suggesting a direct interaction between sensitized lymphocytes and normal bone‐marrow cells in the inhibition of tumor growth.
In vitro effects on tumor cells of macrophages isolated from an early‐passage chemically‐induced murine sarcoma and from its spontaneous metastases
Authors: Mantovani Alberto
Published: February 2007

Macrophages were isolated by adherence from an early‐passage chemically‐induced tumor in C57BL/6 mice and from its spontaneous lung metastases. Cytolytic activity was measured as release of [3H]‐thymidine from prelabelled tumor cells and cytostasis in a post‐labelling assay. Normal, unstimulated peritoneal mac‐rophages exhibited low but significant non‐specific cytotoxic activity at attacker to target (A:T) ratios ≧ 20:1, whereas stimulation of tumor‐cell proliferative capacity was consistently observed at A:T ratios ≦ 2:1. Macrophages from the peritoneal cavity of tumor‐bearing mice, from the primary tumor or from pooled secondaries had baseline cytotoxic or growth‐enhancing (depending on the A:T ratio) potential similar to that of control peritoneal macrophages. In vitro exposure to endotoxin, lymphokine supernatants or partially purified fibroblast interferon augmented the tumoricidal activity of normal and tumor‐associated macrophages; tumor‐associated macrophages showed no evidence of enhanced responsiveness to these activating stimuli. Tumor cells from the primary neoplasm and its spontaneous metastases were equally susceptible to macrophage tumoricidal activity. It is inferred from in vitro data that the relatively low numbers of non‐activated macrophages present within poorly immunogenic metastasizing tumors may have no direct effect or actually stimulate tumor‐cell proliferative capacity at the primary tumor site; conversely, disseminating tumor cells might encounter sufficient numbers of mononuclear phagocytes in the circulation and in lungs to permit the expression of macrophage cytotoxicity, at least during the early steps of metastasis formation.
Kinetics of inflammation and sarcoma cell development in primary moloney sarcoma‐virus‐induced tumors
Authors: Becker Susanne , Haskill Stephen
Published: February 2007

The kinetics of ‘sarcoma’ cell appearance and inflammatory cell infiltration into primary Moloney sarcoma virus (MSV)‐induced tumors has been studied in normal and partially immunosuppressed anti‐lymphocyte‐globulin (ALG)‐treated A/WySn mice. The ALG treatment facilitated an earlier appearance of gp70‐positive ‘sarcoma’ cells accompanied by an intense inflammatory response. Time course pulse‐labelling studies showed that a decreasing proportion of gp70‐positive ‘sarcoma’ cells were incorporating [3H]‐thymidine in vivo in both normal and immunosuppressed mice as the lesion progressed to maximum size. ALG‐treated mice inoculated with MSV were given a single injection of [3H]‐thymidine immediately prior to extensive appearance of gp70‐positive ‘sarcoma’ cells (day 6) and were studied for the presence of labelled gp70‐positive cells 2 h, 2 days and 6 days post labelling. The data indicate that few cells divided during the time in which an 8‐ to 10‐fold increase in virus‐positive ‘sarcoma’ cell number occurred. These experiments provide evidence that recruitment rather than proliferation of virus‐positive cells occurred. The results also suggest that, within the tumor, defense mechanisms develop which restrict sarcomacell proliferation also in ALG‐treated mice. The composition of inflammatory cells during the course of tumor progression and regression in the uncompromised mice revealed that the proportion of lymphocytes was highest early and late during tumor development, dropping to a minimum at the peak size of the tumor. Macrophages and granulocytes constituted 70–80% of the total cells recovered at peak tumor size and the onset of regression. In the ALG‐treated mice, the proportions of macrophages, granulocytes, and infrequent lymphocytes remained constant throughout the duration of the tumor progression. A decrease in total cells, including a decrease in gp70‐positive cells, was noticed before a change in the proportion of infiltrating lymphocytes occurred due to recovery of the immune system. The composition of the inflammatory cells at onset of regression suggests that macrophages and granulocytes are of major importance in the defense against MSV infection.
Systemic and in situ natural killer and suppressor cell activities in mice bearing progressively growing murine sarcoma‐virus‐induced tumors
Authors: Gerson J. M. , Varesio L. , Herberman R. B.
Published: February 2007

The activity of systemic and in situ natural killer (NK) cells was measured in 3‐ to 5‐week‐old CBA mice with progressively growing murine sarcoma virus (MSV)‐induced tumors. Splenic NK activity was depressed in tumor‐bearing mice. NK activity was quite low or not detectable in unfractionated cell suspensions from the tumors 10–12 days after inoculation of virus, but activity was observed upon depletion of phagocytic and/or adherent cells. To determine whether this in situ inhibition of NK activity was correlated with the presence of previously described suppressor cells, subpopulations of cells from the tumors were tested for their ability to suppress various responses of normal spleen cells: NK activity, lymphoproliferative responses to concanavalin A, and proliferation‐independent production of macrophage inhibition factor. A similar pattern of suppressor activity was seen in all of the assays, indicating the presence of pleiotropic suppressor cells in progressively growing MSV‐induced tumors.
Extravascular natural cytotoxicity in man: Anti‐K562 activity of lymph‐node and tumour‐infiltrating lymphocytes
Authors: Moore M. , Vose B. M.
Published: February 2007

A major distinction is reported between the cytolytic activity of peripheral blood lymphocytes (PBL) and that of lymph‐node and tumour‐infiltrating lymphocytes (TIL) against targets of the NK‐sensitive K562 cell line in short‐term 51Cr release assays. In the PBL of normal donors and lung cancer patients in whom disease was advanced anti‐K562 reactivity, though variable, was consistently detectable and this activity could be augmented to a similar extent in patients and controls by treatment of effectors with exogenous interferon (IF). By contrast anti‐K562 activity in lymph‐node cells (LNC) and TIL was virtually absent and significant levels could not be induced by exposure to IF. This activity was not attributable to coexistent suppressor cells for NK function since admixture of LNC and TIL with normal PBL failed to modulate K562 killing by the latter. The results imply that K562‐reactive NK cells and their precursors may frequently be present at sub‐threshold levels in the lymph nodes of tumour‐bearing patients and a similar explanation could account for the inactivity of TIL. However, in the latter situation, actively‐induced NK dysfunction in situ incapable of regeneration by IF, and attributable to as yet undefined tumour‐associated factors, may also be involved.
Tumor biopsy cells participating in systems in which cytotoxicity of lymphocytes is generated. Autologous and allogeneic studies
Authors: Vánky F. , Argov S. , Klein E.
Published: February 2007

Freshly separated tumor cells from sarcomas and carcinomas were used in various roles in lymphocyte‐target cell interaction assays. They were poorer allogeneic stimulators than lymphocytes. They were however good allotargets for the cytotoxicity generated in mixed lymphocyte cultures. They were also killed as third party targets by lymphocytes activated in MLC. In a proportion of experiments, lymphocytes activated in MLC killed autologous tumor cells. Autotumor killer effect was generated in the majority of mixed cultures containing lymphocytes and tumor biopsy cells from the same individual. Generation of cytotoxicity against K562 was a good measure of lymphocyte activation and could be used as a sensitive indicator for the occurrence of the recognition step in the mixed cultures. We propose that for the search of lymphocytes with specific receptors, activation is a more reliable parameter than specific cytotoxicity since the latter function is also influenced by the sensitivity of the target. The results confirmed that patients with carcinomas and sarcomas possess autotumor‐reactive lymphocytes. These can be activated for cytotoxicity by in vitro confrontation with the tumor cells and occasionally through stimulation which is unrelated to the tumor cells.
Lymphocyte‐dependent antibodies to antigen 3.1, a cell‐surface antigen expressed by a subgroup of human melanomas
Authors: Hellström Ingegerd , Hellström Karl Erik , Yeh Ming‐Yang
Published: February 2007

Previous work from our laboratory has led to the isolation of a monoclonal IgG2a mouse antibody, 3.2, which is specific for an antigen, 3.1, that is strongest expressed by a group of human melanomas. We have now demonstrated that this antibody can mediate antibody‐dependent cellular cytotoxicity (ADCC) to human melanoma cells expressing antigen 3.1, and that lymphocytes from human peripheral blood can be used as the source of K cells. A monoclonal IgG1 antibody, 3.1, to the same determinant of antigen 3.1 gave only weak and inconsistent ADCC.
Spontaneous cytogenetic abnormalities in lymphocytes from thirteen patients with ataxia telangiectasia
Authors: Taylor A. M. R. , Oxford J. M. , Metcalfe J. A.
Published: February 2007

Ataxia telangiectasia (AT) is a human autosomal recessive disorder in which patients show a marked predisposition to malignant disease and cytogenetic abnormalities. We report here the levels of spontaneously occurring chromosome aberrations and particularly the presence of cytogenetically marked clones of cells in peripheral lymphocytes of 13 patients. There is a variation between the patients with respect to frequency of different aberration types, and clones are present in 5/13 patients. Several of these patients appear to have more than a single clone, possible clones or subclones. There is no evidence for any malignant disease in any of these patients. A description is given from one of these patients, of the most complex clone so far reported in an AT patient without malignant disease. The development of such a complex clone might be important as a step in malignant change. Similarities between this clone and one reported in an AT patient with T‐cell chronic lymphocytic leukaemia are discussed.
Demonstration of the transferrin receptor in human breast cancer tissue. Potential marker for identifying dividing cells
Authors: Shindelman Jeffrey E. , Ortmeyer Ann E. , Sussman Howard H.
Published: February 2007

A transferrin receptor was demonstrated in tumor tissue from 10 patients with breast carcinoma and one patient with breast sarcoma. Binding studies were conducted by measuring the amount of 125I‐transferrin binding to microsomal preparations of the tumor tissue. Elevated levels of specific transferrin binding were found in the tumors with a range of 11–35% of bound transferrin, whereas microsomes prepared from non‐neoplastic breast tissue samples bound only 2.3% and 2.4% of the transferrin. Scatchard analysis of binding studies conducted with tissues from a breast cancer and from a breast sarcoma indicate that the receptor has a Ka = 9.0 × 108M. The binding site is specific for transferrin, as studies show that non‐radioactive transferrin displaced labelled transferrin, while human IgG and human albumin did not. The receptor‐transferrin complex was precipitated from a detergent extract of the breast sarcoma with antiserum to human transferrin. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the immunoprecipitate gave a polypeptide of Mr 90,000 daltons, which is of similar molecular weight found for the putative transferrin receptor in all of a series of human cultured cell lines previously examined.
Carcinomas induced by cell lines cultivated from normal mouse placentas
Authors: Log T. , Chang K. S. S. , Hsu C.
Published: February 2007

Cell lines have been established from placentas of various strains of mice by in vitro cultivation. The established lines appear to be trophoblast cells as judged from their production of gonadotropin‐like substance and steroid hormones. The cell lines lack detectable H‐2 antigen, Fc receptor sites, Thy I antigen and surface immunoglobulin determinants. In addition, the cells are resistant to murine type‐C RNA tumor virus infection. The resistance is due to a block of viral replication after the stages of viral adsorption and penetration. The cell lines induced carcinomas after injection into adult mice of original host strains. Usually at least 2 × 106 cells are required to induce tumors by i.p. or s.c. injection. Transplantation of the tumor cells to various strains of mice revealed that some strains accepted and some strains rejected the transplant. Genetic crossings between susceptible and resistant mouse strains indicate that susceptibility to transplantation of tumor is determined by a single pair of dominant autosomal genes.
Genetic resistance to herpesvirus‐induced lymphoma at the level of the target cell determined by the thymic microenvironment
Authors: Gallatin W. Michael , Longenecker B. Michael
Published: February 2007

The mechanisms responsible for non‐major‐histocompatibility‐complex (MHC)‐associated genetic resistance to Marek's disease (MD) were studied in resistant line 6 and susceptible line 7 chickens. Adoptive transfer of specific‐pathogen‐free (SPF) adult spleen cells from the susceptible line into irradiated 8‐day‐old resistant recipients significantly increased MD mortality following contact exposure to Marek's disease virus (MDV). No protective effect was observed following transfer of spleen cells from line 6 donors into susceptible line 7 recipients. Lymphocytes from the susceptible line 7 were shown by earlier experiments to have a higher capacity to adsorb the herpesvirus of turkeys (HVT). Fragments of thymic stroma from line 6 and line 7 were grafted onto the chorioallantoic membrane (CAM) of line 6 embryos. Following revascularization and repopulation of the grafts with lymphocytes of resistant host origin, the virus adsorption capacity of the non‐lymphoid stromal and lymphoid portions of the grafts was assayed in vitro by focus inhibition. While no difference in adsorption was observed between the line 6 and line 7 donor origin stromal cells, significantly more virus was adsorbed by the repopulating line 6 lymphoid cells harvested from the susceptible line 7 grafts than by line 6 lymphocytes from syngeneic line 6 grafts. The genotype of the thymic microenvironment was, therefore, found to be a determining factor in the expression of the high virus‐binding phenotype. Virus neutralizing monoclonal antibodies against HVT were prepared and used in the new in vitro antibody‐directed rosetting assay (ADRA) to determine the frequency of virus‐binding cells in the lymphoid organs of these two lines. Virus‐binding leukocytes were more frequent in the line 7 susceptible birds. In a time‐course study, following reconstitution of irradiated, third‐party, histocompatible recipients with SPF line 7 spleen cells, a sharp increase in MDV‐infectious centres was observed in peripheral blood at day 17 post exposure. A decrease in infectious centres was observed, however, at the same time point in recipients of line 6 spleen cells. The explanation for the difference in MD mortality seen in line 6 and line 7 is, thus, complex and may reflect separate resistance mechanisms which operate at more than one level. First, resistance is manifested at the level of a direct interaction between MDV and its target T lymphocyte with the thymic microenvironment playing a key role in the event. Second, and later during the course of infection, genetic variation in the capacity for immune surveillance against MDV‐infected and/or transformed cells may come into play. Whether these two properties segregate independently or not has yet to be determined.
Clonal variation and functional correlation of organ‐specific metastasis and an organ‐specific metastasis‐associated antigen
Authors: Shearman P. J. , Longenecker B. M.
Published: February 2007

Monoclonal antibodies were used to probe the cell surface of organ‐selected metastatic variant cells. Previously we defined a liver metastasis‐associated antigen (LMAA) by means of the reaction of a monoclonal antibody with a liver metastasis selected tumour variant cell line, MDCC‐AL2. The monoclonal anti‐LMAA antibodies specifically inhibit liver metastasis of AL2. There is a correlated, clonal variation in LMAA expression and liver metastasis in both the AL2 cell line and an overy‐selected metastatic variant MDCC‐AL3. The variation in liver metastatic ability is thought to represent clonal progression of the tumour cell lines. The LMAA probably represents only one of the ways in which a tumour cell may give rise to a liver metastasis. Two hypotheses are discussed utilizing the LMAA in a functional role in the specific trapping of metastatic tumour cells in the liver or the successful colonization of the liver by metastatic tumour cells.
Inter‐individual differences in oxidative benzo(a)pyrene metabolism by normal and tumorous surgical lung specimens from 105 lung cancer patients
Authors: Sabadie N. , Richter‐Reichhelm H. B. , Saracci R. , Mohr U. , Bartsch H.
Published: February 2007

Oxidative benzo(a)pyrene (BP) metabolism was studied in 12,000 g(S12) supernatant fractions of surgical lung specimens obtained from lung cancer patients undergoing surgical resection. Arylhydrocarbon (BP)hydroxylase (AHH) activity was determined in both normal and tumorous lung tissue specimens from the same patient. A more than 20‐fold inter‐individual variation in AHH activity was found in both the normal and the tumorous lung tissue samples investigated. The apparent KM of the pulmonary enzyme (1–2.5 × 10−4 M) was identical in tumorous and normal tissue. High‐performance liquid chromatography (HPLC) of ethyl acetate‐extractable BP metabolites from the normal lung tissue of six patients identified phenols, dihydrodiols and quinones of BP. The mean yields of these metabolites were very similar to those obtained in assays in the presence of lung S12 from BDVI rats, except that more trans−9, 10‐dihydro‐9, 10‐dihydroxy‐BP (BP‐9, 10‐diol) was formed in the presence of human lung S12. The formation of 3‐hydroxy‐BP (3‐HO‐BP) and BP‐9, 10‐diol in human lung specimens, however showed variations up to 7‐ and 13‐fold, respectively. In normal lung specimens, the total amounts of 3‐HO‐BP and 9‐HO‐BP formed correlated positively with the total amounts of trans‐7, 8‐dihydro‐7, 8‐dihydroxy‐BP (BP‐7, 8‐diol), BP‐9, 10‐diol and trans‐4, 5‐dihydro‐4, 5‐dihydroxy‐BP (BP‐4, 5‐diol) formed (r = 0.83; p < 0.05). A positive correlation was also found between the AHH activity in normal and tumorous tissue from all cancer patients (r = 0.24; p < 0.05). The ratio (R) of AHH activity in tumorous tissue to that in normal tissue from the same lung cancer patient was < 1 in 73 patients, 1 in 2 patients, and > 1 in 11. In 7 of 10 subjects who underwent surgical resection for suspected lung tumours, but in whom histological analysis revealed no malignant tissue, R was > 1 for the AHH activity in the inflammatory tissue to that in normal tissue. The observation of consistently lower AHH activity in malignant lung tissue parallels findings in hyperplastic liver nodules induced in rats by hepatocarcinogens. The frequency distribution of pulmonary AHH activity in normal and tumorous tissue from 105 lung cancer patients, with all types of tumours, was compatible with a unimodal distribution of the enzyme activity. In a subset of 43 patients with squamous‐cell carcinoma, the same distribution was seen; in those patients, AHH activity in tumorous tissue correlated negatively (r = −0.18; p > 0.10) with the number of cigarettes smoked per day prior to surgery. No differences were observed between the mean values for AHH activity in cases of squamous‐cell carcinoma and those of adenocarcinoma. No relationship was found between AHH activity in normal or tumour tissue and the age of patients. Whether differences in pulmonary AHH activity represent a host risk factor in persons who smoke remains to be investigated.
Special report animal species in which n‐nitroso compounds induce cancer
Authors: Bogovski P. , Bogovski S.
Published: February 2007

In reviews on the carcinogenicity of N‐nitroso compounds (NC) the number of animal species in which these compounds induce cancer is understated. In recent years additional species have‐been used in experiments. Tumours have been induced by NC in 39 species which belong to 36 genera, 25 families, 17 orders and five classes of animals. The names of these taxa are presented in Latin and the common names of species are given in English, French and German. The carcinogenic action of eight NC in various species is tabulated.
Cell‐mediated suppression of tumor immunity has a non‐specific component. I. Evidence from transplantation tests
Authors: Hellström Karl Erik , Hellström Ingegerd
Published: February 2007

We have first demonstrated that the growth of a transplanted, 3‐methyl‐cholanthrene‐induced BALB/c sarcoma, MCA‐1425, in specifically immune syngeneic mice, was facilitated when the MCA‐1425 tumor cells were injected together with either a mixture of irradiated MCA‐1425 cells and thymus cells from mice immune to MCA‐1425 or a mixture of irradiated cells from an antigenically different BALB/c sarcoma, MCA‐1460, and thymus cells from mice immune to MCA‐1460. We then performed Winn assays to study the induction of an immune response that could prevent the outgrowth of MCA‐1425 cells in irradiated syngeneic recipients. Tumor immunity was found to be suppressed, if the mice immunized by a subcutaneous transplant of MCA‐1425 cells and used as lymphocyte donors, were injected intraperitoneally with cells from either a different sarcoma, MCA‐1460, or from 12‐day BALB/c embryos. We tentatively attribute our findings to antigen‐non‐specific suppressor effector cells and postulate that an antigen‐specific event is often involved in their induction.
Effect of solvents on methylcholanthrene‐induced carcinogenesis in mice
Authors: Reddy A. Lakshma , Fialkow Philip J.
Published: February 2007

We have shown previously, with X‐chromosome linked phosphoglycerate kinase (PGK) cell markers, that the fibrosarcomas induced in mice by subcutaneous injection of 0.2–2.0 mg of methylcholanthrene (MCA) dissolved in olive oil had a multicellular origin. In this study we used a constant dose of MCA injected subcutaneously and compared the effects on tumorigenesis of using benzene or olive oil as the solvents. The benzene and olive oil groups differed in tumor incidence (100% versus 50%), location (muscle versus skin), and type (rhabdomyosarcomas versus fibrosarcomas). Each of the nine olive‐oil MCA‐induced tumors showed both PGK enzyme types, whereas 13 of 16 tumors induced by MCA in benzene displayed only a single PGK type. This difference in PGK phenotypes suggests that the MCA‐benzene neoplasms arose from one or a few cells. We conclude from these results that the nature of the solvent plays an important role in the type and number of cells from which tumors induced by subcutaneous injection of MCA arise.
Carcinogenicity of analgesics: Long‐term treatment of sprague‐dawley rats with phenacetin, phenazone, caffeine and paracetamol (acetamidophen)
Authors: Johansson Sonny L.
Published: February 2007

Six groups of male Sprague‐Dawley rats were treated with phenacetin, phenazone or caffeine in the diet or with combinations of these chemicals. Another group received paracetamol in the diet and a further group received only the control diet. The rats were treated for up to 117 weeks. Renal pelvic tumors were only seen in rats treated with phenacetin or phenazone alone or in combination with caffeine, phenazone having slightly greater activity toward the urinary tract than phenacetin. Phenacetin, however, had a greater overall carcinogenic effect, inducing 31 malignant tumors. The urinary tract and the kidneys had the highest incidence of tumor followed by squamous‐cell carcinomas of the head and neck. Half of the rats treated with phenacetin, phenazone and caffeine in combination developed hepatomas. The explanation may be that the addition of phenazone and caffeine altered the metabolism of phenacetin, increasing the production of N‐hydroxy‐phenacetin, a known liver carcinogen. The justification of using phenacetin as a human analgesic must be seriously questioned, and further studies with phenazone are required.
Susceptibility to killing by bcg‐activated macrophages associated with ‘spontaneous’ neoplastic transformation in culture
Authors: Tucker Robert W. , Meltzer Monte S. , Sanford Katherine K.
Published: February 2007

Non‐tumorigenic and ‘spontaneously’ transformed tumorigenic paired cell lines derived from mouse, rat, or hamster embryonic tissues were examined for their susceptibility to killing by mouse peritoneal macrophages activated in vivo by infection with Mycobacterium bovis, strain Bacillus Calmette‐Guérin (BCG). Susceptibility to killing was measured by the extent of clearing in a confluent layer of target cells overlying an area of adherent macrophages or by the release of 3H counts from target cells prelabelled with [3H]‐thymidine. Only tumorigenic lines showed complete clearing by activated macrophages; the reaction occurred regardless of species differences between macrophages and target cells. The degree of clearing increased with increasing ratio of macrophages to target cells. Normal macrophages from uninfected mice did not produce a clearing reaction. The macrophage reaction discriminated between non‐tumorigenic and tumorigenic cells with short tumor latent periods (<100 days) even when neoplastic and non‐neoplastic cells were derived in culture from the same cell. The more tumorigenic lines (i.e., shortest latent period) tended to be more susceptible to killing. Thus, cells spontaneously transformed in culture are more susceptible to killing by activated macrophages than are their non‐neoplastic counterparts. In two cloned lines the enhanced susceptibility to macrophage killing appeared to be a late manifestation of the neoplastic change.
Reactivation of epstein‐barr virus‐specific cytotoxic t cells by in vitro stimulation with the autologous lymphoblastoid cell line
Authors: Rickinson A. B. , Moss D. J. , Allen D. J. , Wallace L. E. , Rowe M. , Epstein M. A.
Published: February 2007

Unfractionated mononuclear (UM) cells and T cells freshly prepared from the blood of adult donors were co‐cultivated in microtest plate wells with progressively lower numbers of cells from the autologous EB‐virus‐transformed B‐cell line. The fresh cells present in co‐cultures from EB virus antibody‐negative (seronegative) donors regularly facilitated autologous cell line outgrowth, monitored after 4 weeks, whereas outgrowth was markedly inhibited in the corresponding co‐cultures from seropositive donors. Larger‐scale co‐cultures, set up at a ratio of 80–100 fresh UM cells to one autologous virus‐transformed B cell, were harvested after 8 to 12 days and the T‐cell subpopulation was examined for cytotoxicity both by growth inhibition and by chromium release assays. Cytotoxic T cells were generated exclusively in seropositive donor co‐cultures and were strongly active against the autologous virus‐transformed cell line without affecting either autologous uninfected B cells or any of a range of EB virus genome‐negative target cell lines chosen as sensitive indicators of non‐specific cytotoxicity. Recognition of allogeneic EB‐virus‐transformed cells was restricted to those whose HLA‐A and/or B and/or C antigen expression matched that of the effector cells themselves; moreover target cell lysis was specifically inhibited in the presence of monoclonal antibodies binding to these HLA antigens. The results indicate that EB‐virus‐specific HLA‐restricted memory T cells, present in the blood of previously‐infected individuals, can be reactivated in vitro using the established autologous virus‐transformed cell line as a stimulus. The reactivated cytotoxic cells appear to recognize a virus‐induced lymphocyte‐detected membrane antigen, LYD‐MA, analogous to that first invoked to explain the cytotoxic response to primary EB virus infection observed during infectious mononucleosis.
in vitro motility of cells from human epidermoid carcinomas. a study by phase‐contrast and reflection‐contrast cinematography
Authors: Haemmerli Gisela , Str Peter
Published: February 2007

The motile behavior of six cell lines derived from human squamous carcinomas (two from the larynx, four from the tongue) was studied by cinematography under phase‐ and reflection‐contrast illumination. The recorded cell activities consist in spreading, stationary and translocative motility, and aggregate formation. Within this common pattern, quantitative modifications (≪sub‐patterns ≪) are stable properties of the individual cell lines. Such modifications are particularly evident with regard to the dynamic texture of the aggregates which ranges from loose, netlike structures to compact islands with smooth borders. Accordingly, the intensity of cell traffic within and around the aggregates varies considerably. It is discussed to what extent the in vitro motility of the carcinoma cell populations reflects their behavior in the organism and thus the significance of cell movements for invasion.
Characterization of human keratinocyte
Authors: Peehl Donna M. , Stanbridge Eric J.
Published: February 2007

Intraspecific human cell hybrids were created by fusing normal epidermal keratinocytes with carcinoma (HeLa) cells. All of the hybrids were epithelial in morphology and exhibited a bright cytoskeletal pattern after indirect immunofluorescent labelling by antibody against keratin. Like the normal parental cells, the hybrid populations had organized arrays of microfilaments, and expressed low levels of surface fibronectin, predominantly in short ≪stitches ≫ at cell boundaries. None of the cells expressed collagen type I, as expected of epithelial cells. Subcutaneous injection into nude mice revealed that the tumorigenic phenotype was initially suppressed in certain of the hybrids. However, cells of these lineages tested at later population doublings, and other hybrid clones tested at early population doublings, formed very small, non‐progressive nodules. Histologically, these nodules resembled moderately to well‐differentiated squamous‐cell carcinomas. The properties in vitro and in vivo of these epithelial hybrids are compared to those of human fibroblast × HeLa hybrids.
Alkaline phosphatase expression in human cell lines derived from various malignancies
Authors: Benham Frances J. , Fogh Jørgen , Harris Harry
Published: February 2007

A search for expression of heat‐stable placental‐type alkaline phosphatase (ALP) has been carried out in 19 unselected human tumor cell lines, known not to be HeLa. All cell lines showed measurable ALP activity and in 15 of the lines at least low levels of a heat‐stable, presumptively placental‐type ALP were detected. In five of these lines where the level of this heat‐stable activity was sufficient, further investigation (immunologic, inhibition and electrophoretic studies) demonstrated that this ALP was placental‐type in its characteristics and clearly different from liver/bone/kidney or intestinal ALPs. In 10 lines the heat‐stable activity was too low to allow further characterization. In four lines no heat‐stable activity could be detected. The thermolabile ALP activity in these various lines was liver/bone/kidney in type. This study suggests that the placental ALP locus may be expressed at least at low levels in a much higher proportion of tumors and tumor cell lines than previously reported. The findings, taken together with recent reports that low levels of placental‐type ALP are present in some normal adult tissues (cervix, Goldstein et al., 1980; testis, Chang et al., 1980), indicate that so‐called ‚ectopic’︁ synthesis of placental ALP in tumor cells may not necessarily be due to derepression of a structural locus which is completely unexpressed in normal adult tissues. It may represent an enhancement of expression in malignancy or there may be clonal expansion of a particular cell type which normally expresses the alkaline phosphatase at a high level.
Murine embryonal carcinoma cells: Universal targets for mammalian nk cells?
Authors: Stern Peter , Gidlund Magnus , Kimura Arthur , Gr Kjell‐Olov , Wigzell Hans
Published: February 2007

Natural killer (NK) cells from mice lyse murine teratocarcinoma stem cells in accordance with their appropriate cellular, genetic and interferon inducible features. In addition, rat and human putative NK cells were found to exhibit cytotoxicity of these embryonal carcinoma stem cells. By contrast, endodermal cells derived from such stem cells, either as cell lines or by recent induction with retinoic acid, were relatively resistant to effectors from all three mammalian species tested. Attempts to elicit a murine T‐cell response to embryonal carcinoma by secondary in vitro stimulation failed. As previously shown, T killers directed to H‐2 determinants were unable to lyse the MHC lacking embryonal carcinoma cells. The use of lectin ‘glues’, a procedure supposedly capable of revealing the total cytotoxic T‐cell potential regardless of specificity, also failed to elicit lysis of these target cells. We have therefore failed to find evidence for T‐cell recognition or lysis of embryonal carcinoma while NK cells from different species seemingly regard these latter cells as ‘universal’ targets.
Comparative antineoplastic activity against p388 leukemia of 9‐β‐d‐arabinofuranosyladenine (area) and 9‐β‐(2′‐azido‐2′‐deoxy‐d‐arabinofuranosyl)adenine (arazide)
Authors: Lee Sang H. , Thomas Linda K. , Unger Frank M. , Christian Rudolf , Sartorelli Alan C.
Published: February 2007

The anticancer effects of 9‐β‐(2′‐azido‐2′‐deoxy‐D‐arabinofuranosyl)adenine (arazide) were compared to those of 9‐β‐D‐arabinofuranosyladenine (araA) in P388 leukemia cells. Arazide was less susceptible than araA to deamination by a partially purified preparation of adenosine deaminase from P388 cells. This corresponded to significantly more cytotoxicity by arazide than by araA to P388 cells in culture; however, neither agent prolonged the survival time of mice bearing this experimental tumor. Coadministration of these agents with an inhibitor of adenosine deaminase, 2′‐deoxycoformycin (2′dCF), led to marked antineoplastic activity with arazide. Thus, daily administration of arazide (12.5–25 mg/kg per day) with 2′dCF (0.25 mg/kg per day) for 6 consecutive days to mice bearing the P388 leukemia resulted in 50% of the animals surviving for at least 50 days. In combination with 2′dCF, arazide levels higher than 25 mg/kg per day × 6 showed host toxicity as expressed by major loss in body weight and by decreased survival times of leukemia‐bearing mice. AraA plus 2′dCF in the same regimen produced only slight increases in survival time. [3H]‐Thymidine incorporation into DNA of P388 cells was inhibited by more than 90% following administration of a therapeutic dose of arazide and 2′dCF to leukemia‐bearing mice, and inhibition of the formation of DNA persisted for at least 24 h. Under the same experimental conditions, araA and 2′dCF caused less inhibition of DNA biosynthesis and more rapid recovery occurred. Neither arazide nor araA caused inhibition of incorporation of radioactive uridine or leucine into acid‐insoluble material. The results indicate that arazide, which is considerably more water‐soluble than araA, is also superior to araA as an antineoplastic agent when employed in combination with 2′dCF on a once‐a‐day schedule × 6, and suggest that this action is the result of potent and long‐lasting inhibition of DNA synthesis.
Androgen, estrogen and progestin binding sites in human leukemic cells
Authors: Danel Laurence , Martin Pierre , Escrich Edouard , Tubiana Nicole , Fiè Denis , Saez Simone
Published: February 2007

Sex steroid binding capacity was investigated in malignant cells from 32 patients with acute non‐lymphoblastic leukemia (25 patients with acute myeloid leukemia, 4 with subacute leukemia, 3 with chronic myeloid leukemia in blast crisis) and 30 patients with acute lymphoblastic leukemia. Specific binding of labelled steroids was characterized either by competition assay in cytosol fraction or by whole‐cell incorporation. In some cases further characterization of the receptor complex was attempted by sucrose gradient centrifugation and gel filtration column. The results show the presence of specific binding sites for dexamethasone (22/32 in non ALL and 30/30 in ALL), for estrogens (11/15 in non‐ALL and 5/12 in ALL), for progestins (8/25 in non‐ALL and 5/13 in ALL) and for androgens when RI881 was used as ligand (8/21 in non‐ALL and 5/10 in ALL patients) but only in 1/13 non‐ALL patients and no ALL patients when labelled 5α DHT was used. These results indicate that the blast cells from patients with acute leukemia contain specific proteins binding steroids with a high affinity. Our results for dexamethasone receptors are similar to those described in the literature in ALL and non‐ALL.
Extracellular matrix proteins characterize human tumor cell lines
Authors: Alitalo Kari , Keski‐oja Jorma , Vaheri Antti
Published: February 2007

Extracellular matrix proteins synthesized and secreted by adherent human tumor cell lines were analyzed using metabolic labelling with glycine and proline in the presence of ascorbate, polypeptide analysis by polyacrylmide gel electrophoresis, affinity chromatography, collagenase digestion, and immunofluorescence staining. The results showed a characteristic pattern of matrix proteins for each tumor cell type. Tumor cell lines of mesenchymal origin produced mostly interstitial types (I and III) of collagen and fibronectin. Carcinoma cell lines secreted only basement membrane proteins, type IV collagen, laminin and fibronectin, but not interstitial collagens. A melanoma and a rhabdomyosarcoma cell line produced type V of procollagen that has not previously been described in cell culture. Neuroblastoma cells were shown to be phenotypically heterogeneous also with respect to matrix protein production. We propose that the analysis of extracellular matrix proteins may serve as an adjunct in the classification of human tumors.