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Biomedical subjects

A S Rabson

Publications and source records attributed to A S Rabson.

At least 19 recordsLinked to original sources

Characterization and tumorigenicity of a butyrate-adapted T24 bladder cancer cell line.

We have adapted T24P, a tumorigenic subline of the T24 human bladder cancer cell line, to grow in 5 mM butyrate. In the presence of butyrate, the adapted cells (T24P/B) grow more slowly than the unadapted cells (T24P/C), have a lower saturation density, increased serum requirement for growth, loss of ability to form colonies when plated at low cell density, and decreased ouabain sensitivity. Morphologically, T24P/B cells in butyrate are large and flattened with increased cytoplasm. When T24P/B cells are grown without butyrate, the morphological changes, growth rate, plating efficiency, and ouabain sensitivity return to those of T24P/C. While the saturation density increases, it does not return to levels of T24P/C, and the size of colonies never reaches that of the T24P/C colonies. Both T24P/C and T24P/B are tumorigenic in nude mice, however, the T24P/B tumors differ grossly and microscopically from those produced by T24P/C in that they contain large cystic structures filled with clear fluid and lined by transitional cell epithelium with flattened surface layers. Although the transformed phenotype and tumorigenicity of T24P are modified by adaptation to growth in butyrate, no significant changes in ras oncogene RNA or protein expression were identified.

Acetylation

Tumorigenicity of T24 urinary bladder carcinoma cell sublines.

Two sublines of the T24 human urinary bladder carcinoma cell line which differ in tumorigenicity in nude mice have been studied (T24A and T24P). T24A obtained directly from the American Type Culture Collection is non-tumorigenic while T24P obtained after multiple passages in several NCI laboratories produces tumors in 100% of inoculated mice. T24P cells differ morphologically from T24A, have a higher saturation density, are less serum-dependent for growth, and are more sensitive to ouabain toxicity. Cytogenetic studies show that the 2 sublines differ significantly in chromosome number, with a modal chromosome range of 76-89 in T24A and a modal chromosome number of 48-51 in T24P. Southern blot analysis of MspI cleaved T24A and T24P DNAs with the H-ras SmaI probe indicates that both contain only the activated mutant allele originally described in T24. Northern blot analysis shows equal amounts of the 1.2kB ras polyadenylated message, and immunoblotting with rasHa antibody demonstrates no significant difference in the amounts of ras proteins. These results indicate that 2 sublines of a ras oncogene-containing tumor cell line can differ greatly in tumorigenicity and other in vitro characteristics of transformation, and yet have similar expression of the ras oncogene. The fact that the tumorigenic cell line contains fewer chromosomes suggests that tumorigenicity may be related to the loss of some regulatory gene.

Animals

Human cytomegalovirus (HCMV) enhances bovine papilloma virus (BPV) transformation in vitro.

Infection of NIH 3T3 cells with a combination of HCMV and BPV resulted in more foci than infection with BPV alone. Foci were microscopically apparent at 4 days in the mixed infection and did not appear until 2 days later in the cultures infected with BPV alone. The enhancement was abolished by heat inactivation of the HCMV and also when the HCMV was replaced by a "mock inoculum." Southern blot analysis of cellular DNA from transformed cells showed a similar amount of extrachromosomal BPV DNA in cells infected by BPV alone and in cells co-infected with HCMV. No HCMV antigens could be found in these cells by immunofluorescence. The mechanisms of the enhancement are not known. Stimulation of host DNA synthesis by HCMV could possibly increase the transforming efficiency of BPV. Alternatively, the increase in BPV transforming efficiency could be due to a transient increase in BPV-1 transcription by an HCMV transcriptional transactivation factor. Since both HCMV and human papillomaviruses are commonly found in the uterine cervix, HCMV may play a role in human cervical cancer by enhancing the carcinogenic potential of human papillomavirus.

Animals

Further studies on the Mycoplasma pneumoniae extract: ciliostatic and cell recruitment activities.

Since inactivated vaccines have proved disappointing in preventing Mycoplasma pneumoniae disease, we have initiated studies to identify protective immunogens as candidates for an acellular, purified component vaccine. A cell-free extract was prepared, and was shown to have hemagglutination, attachment inhibition, and ciliostasis activities. Ciliostatic activity in hamster tracheal organ cultures was dependent on the time of incubation and on the amount of added extract. The ciliostatic factor was resistant to boiling and to trypsin and chymotrypsin digestion. When administered intratracheally to Golden Syrian hamsters, the extract induced lung lesions with histopathologic characteristics similar to those caused by virulent M. pneumoniae infection. Thus, in addition to attachment and ciliostatic factors, the extract contains factors that induce inflammatory responses in hamster lungs and cause cytotoxic damage to lung tissues.

Animals

Latent infection by herpes simplex virus.

The experimental evidence contributing to the understanding of herpes simplex virus latent infection has been reviewed. The site of residence of the virus during silent periods of the disease appears to be, in the majority of instances, the sensory ganglion innervating the territory of prime infection. Little is known about the factors that bring about latent infection, maintain it, and regulate the production of infectious particles that cause recurrences.

Adolescent

Ultrastructural concomitants of sodium butyrate-enhanced ectopic production of chorionic gonadotropin and its alpha subunit human bronchogenic carcinoma (ChaGo) cells.

Sodium butyrate treatment of cultures of ChaGo (human lung cancer) cells resulted in increased production of human chorionic gonadotropin (hCG) and its alpha subunit (hCG-alpha) and induced a variety of morphologic changes. Elongation and flattening of cells were seen by light microscopy. Immunocytochemistry with antisera against hCG and against hCG-alpha showed an increase in cells containing stainable hCG-alpha. Scanning electron microscopy demonstrated enhanced adhesion of cells to glass cover slips, with elongation, flattening, and decreased cytoplasmic blebs. Ultrastructural changes were examined by transmission electron microscopy and evaluated quantitatively by an unbiased observer. Significant findings included increases in perinuclear tonofilaments, smooth endoplasmic reticulum vesicles, dense mitochondrial inclusions, and lipid granules, as well as decreases in intercellular desmosomes, free polyribosomes, mitochondrial dense granules, and Golgi complexes. The most notable change, a marked decrease in condensed chromatin clumps, may have reflected a butyrate-induced biochemical modification of chromatin leading to enhanced accessibility of certain genes for transcription.

Butyrates

Rejection of adenovirus 2-transformed cell tumors and immune responsiveness in Syrian hamsters.

Transplantation of adenovirus type 2-transformed cell-induced newborn tumor lines to different aged hamsters revealed that the cell-mediated host defenses responsible for tumor graft rejection matured early in the second week of life. When light microscopic examinations were performed during the course of tumor development, the primary histopathological difference between progressing tumors removed from newborn or thymectomized weanling hamsters and regressing lesions from normal weanlings was the lack of an early, mononuclear cell infiltrate in neoplasms from newborn and thymectomized hosts. These results suggest that the maturation of cellular immunity determines resistance to tumor transplantation in this system. This conclusion was supported by the in vitro detection of concanavalin A-responsive lymphocytes in spleens from tumor-resistant suckling but not tumor-susceptible neonatal hamsters. Although the incomplete seeding of thymus-dependent lymphocytes to the peripheral lymphoid tissues of newborn hamsters may partially explain the deficient concanavalin A responses of neonatal spleen cells, there appears to be an additional requirement for a radioresistant, adherent accessory cell population. These findings suggest that the development of a cell-mediated immune response is necessary for the rejection of adenovirus type 2-transformed cells and transformed cell-induced tumors and that this response requires the interaction of T-cells and accessory cell populations.

Adenoviridae

Ewing's sarcoma: an autopsy study.

An autopsy study of 26 cases of Ewing's sarcoma treated with radiation to the primary site plus adjuvant chemotherapy has shown metastatic tumor in 23 cases. Metastases were found typically in lungs, pleura, bones and regional lymph nodes. In three cases no tumor could be found at autopsy, and death was due to complications of treatment. Tumor was found in the irradiated primary site in 13 of the 20 cases in which the primary site was examined at autopsy. Histologically, the tumor at autopsy frequently had increased pleomorphism and increased numbers of bizarre giant cells; however, these changes did not affect the presence of glycogen in tumor cells, thus reaffirming the importance of intracytoplasmic glycogen in the diagnosis of Ewing's sarcoma.

Adolescent

Properties of the cell surface Fc-receptor induced by herpes simplex virus.

Detection of peroxidase-antiperoxidase soluble complexes (PAP) bound to the surface of herpes simplex virus-infected cells has been used to demonstrate virus-induced Fc receptors and to study their distribution. The PAP method is more sensitive than hemadsorption with immunoglobulin-coated sheep red blood cells, and can be used to study localization by light and electron microscopy. Our results indicate that capping takes place after the receptor is engaged by antigen-antibody complexes and that at least a portion of the bound ligand is internalized.

Animals

Hexamethylene bisacetamide induces morphologic changes and increased synthesis of procollagen in cell line from glioblastoma multiforme.

Addition to hexamethylene bisacetamide (diacetyldiaminohexane) to cultures of a malignant mesenchymal cell line derived from a human glioblastoma multiforme induces morphological changes and stimulates the synthesis of procollagen. The morphological changes include cell elongation, an increase of extracellular material with staining properties of collagen by light microscopy, and an increase in extracellular 220-A fibrils by electron microscopy. The rate of procollagen synthesis increased as much as 20-fold, and the ratio of type I:type III procollagen changed, with type I becoming the predominant form. The change in type I:type III ratio is similar to that seen in the maturation of normal fetal to adult connective tissue.

Acetamides

Oncogenicity of a nude mouse cell line transformed by a human papovavirus.

Primary cultures of NIH nude mouse (nu/nu) kidney cells were transformed with a human papovavirus (MMV). The transformed cell line expressed T-antigen, and MMV DNA was found to be associated with the cell DNA. When NIH nu/nu mice were inoculated with the transformed cells, they developed tumors at the injection site but failed to generate detectable levels of T-antibody. A control group of nu/+ littermates rejected the tumor inoculum but mounted an antibody response to T-antigen. It was proposed that nude mouse cells may be a suitable system to test oncogenicity of in vitro transformed cells.

Animals

Lamella-particle complexes in nuclei of owl monkey kidney cells infected with herpesvirus saimiri.

A complex consisting of ribosome-like particles and a striated lamella occurring in stacked, tubular, and twisted ribbon-like configurations was observed in the nuclei of confluent monolayer cultures of primary owl monkey kidney cells infected with Herpesvirus saimiri. They were similar to the cytoplasmic cylindroid structures seen in some human leukemias and in the lymphoma of the northern pike.

Animals

Maintenance of ectopic chorionic gonadotropin and alpha subunit secretion by a human lung cancer cell line (ChaGo) transplanted into nude mice.

ChaGo cells, derived from a human primary carcinoma of the lung, were successfully transplanted into nude mice without any change in morphologic characteristics over four generations and with continued ectopic secretion of human chorionic gonadotropin (HCG) and HCG alpha subunit (HCG-alpha). The concentration of free HCG-alpha was 1,100-fold higher than that of complete HCG in the original ChaGo culture medium but only 35-fold higher in nude mouse plasma, possibly due to slower metabolic clearance of complete HCG. Tumor weights correlated with plasma HCG-alpha but not with HCG. Tumor-bearing mice had significantly heavier uteri than did control mice.

Animals