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At least 199 records · Page 11Linked to original sources
PubMed1979

Tumorgenicity of herpesvirus hominis type 2-transformed cells (line 333-8-9) in adult hamsters.

Inoculation of adult hamsters with greater than 1.5 X 10(2) Herpesvirus type 2 (HSV-2) transformed hamster embryo fibroblasts induced rapidly growing tumours at the site of inoculation, in more than 50 per cent of animals. The tumours were examined by light and electron microscopy, and were histologically anaplastic fibrosarcomas. Lung metastases were frequently found in tumour-bearing animals; these were usually only seen microscopically, and were cytologically similar to the primary tumours. The nature of tumour development showed similarities with naturally occurring tumours of man, and HSV-2 tumour is probably a better model of human cancer than other virus-induced tumours studied in the past.

Animals↗
PubMed1977

Selective growth of transformed cell lines by rat liver perfusate.

Perfused rat liver releases growth-promoting activity for viral, spontaneous, and chemically transformed cells. After 5 days of incubation with perfusate, cell lines 3T12-NY (a spontaneous fibroblast transformant), NQ-T1 (a chemically transformed fibroblast line), W-8 (a chemically transformed epithelial rat liver cell line increase in cell growth above controls. Their respective normal counterparts: 3T3 Cl 42, A31-714, K-16, and HEF are not so stimulated. Within another set, the virally transformed mouse fibroblast cell line, SV3T3, exhibits a 27-fold increase in growth; however, 3T3 (mouse, fibroblasts), Py3T3 (polyomatransformed 3T3 cells), SV-Fl2-101 (a flat revertant line), and SV-Py-3T3 (a doubly transformed line) are nonresponsive. Perfused rat liver also release survival activity for SV-3T3 cells. The growth-stimulating activity in liver perfusate is selective for transformed cells. It is suggested that the liver may play a role in suporting neoplasia in vivo.

Animals↗
PubMed1992

Effect of dibutyryl cyclic AMP and isoproterenol on 7 beta-hydroxycholesterol cytotoxicity and esterification in spontaneous transformed cell lines derived from astrocyte primary cultures.

Incubation of spontaneous transformed cells derived from astrocyte primary cultures with 30 microM 7 beta-hydroxycholesterol (7 beta-OH-CH) which is lethal to the cells or with 150 microM isoproterenol reduces the intracellular level of cAMP (4- and 2-fold respectively). Treatment of the cultures with 0.5 mM dibutyryl (db)-cAMP and 7 beta-OH-CH increases 3-fold the intracellular level of cAMP and both, db-cAMP and isoproterenol, raise the lethal effect of 7 beta-OH-CH and its esterification on C-3-OH by naturally occurring fatty acids (metabolite). Kinetic studies of net steryl-3-esters hydrolysis revealed that db-cAMP and isoproterenol lower that of cholesteryl-3-esters (2-fold) whereas the opposite is found for the metabolite. These data demonstrate that (i) high cAMP intracellular levels modulate differently the net hydrolysis of cholesteryl-3-esters and metabolite, (ii) isoproterenol acts otherwise than cAMP on 7 beta-OH-CH esterification, (iii) the cytotoxicity of 7 beta-OH-CH is linked to its own esterification. The accumulation of metabolite subsequent to db-cAMP or isoproterenol treatment as a result of acyl-CoA:cholesterol acyl transferase activation is discussed.

Animals↗
PubMed2001

Influence of culture conditions on the alpha 1,2-fucosyltransferase and MUC gene expression of a transformed cell line MM-39 derived from human tracheal gland cells.

Human tracheal glands cells (HTGC) in culture are able to respond to adrenergic, cholinergic and purinergic agonists by increasing their serous and mucin secretions. These secretagogues are also able to maintain an optimal responsiveness of serous cells to stimulation when they are regularly and briefly delivered to the cells, making the HTGC a suitable model to study the serous secretion (Merten, in press). Our interest has been focused on the effects of cholinergic and purinergic secretagogues associated to histamine, on the mucous function of the transformed human tracheal gland cell line MM-39, which has a mixed, both serous and mucous, phenotype. When the cells were exposed to short stimulation every 2 days for 3 weeks with 10 or 100 microM carbachol, UTP and histamine, modifications of their mucous phenotype were observed. The expression of MUC genes appeared dependent on the culture conditions. Transcripts of MUC1, MUC4, and MUC5B genes were observed when the cells were regularly exposed to the mixture of secretagogues at a concentration of 10 microM, in contrast to the unstimulated expression of MUC1 and MUC4 in control cells. MUC1, MUC4, MUC7, MUC6 and MUC11 transcripts were observed when the cells were regularly exposed to the mixture of secretagogues at a concentration of 100 microM. These culture conditions were also able to induce an alpha 1,2-fucosyltransferase activity absent in the MM-39 cells cultivated with standard conditions. There was no marked effect on the alpha 2,3-sialyltransferase activity although the expression pattern of the sialyltransferase genes was reduced to the unique presence of ST3Gal III. In conclusion, MM-39 cells exposed to repeated stimulation by secretagogues at different concentrations express different sero-mucous phenotypes.

Animals↗
PubMed1991

Effect of 7 beta-hydroxycholesterol on astrocyte primary cultures and derived spontaneously transformed cell lines. Cytotoxicity and cholesterogenesis.

The correlation between the lethal effect of 7 beta-hydroxycholesterol (7 beta-OH-CH) on spontaneously transformed cell lines derived from rat astrocyte primary cultures (normal cells) and de novo cholesterogenesis was investigated. Both 7 beta-OH-CH and 7-keto-CH were not cytotoxic on normal cells but 7 beta-OH-CH affected markedly the viability of the transformed cells. The use of [14C]acetate or [14C]mevalonate indicated that 7-keto-CH inhibits de novo cholesterogenesis upstream of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) in both cell types whereas 7 beta-OH-CH also inhibits downstream of HMGR. The accumulation of two radiolabelled products X1 and X2 between mevalonate and CH was found in unsaponifiable neutral lipids extracted from 7 beta-OH-CH treated transformed cells. HPLC and GC-MS revealed that X1 and X2 are not lanosterol and 24,25-epoxylanosterol, respectively. Incubation of the transformed cells with X1 and X2 did not affect their viability. Our data demonstrate that, under our experimental conditions, 7 beta-OH-CH cytotoxicity is not linked to the inhibition of de novo cholesterogenesis in cultured glial transformed cells.

Acetates↗
PubMed1978

Growth characteristics in vitro of hybrids between normal and transformed cell lines.

Sensitivity to the inhibition of division during cell crowding in vitro was determined for hybrids between normal and tumor cell populations of human and mouse origin. Interspecies hybrids were more sensitive to cell crowding than intraspecies hybrids. The results suggest that the inhibition of cell division due to crowding was more dependent upon the species of origin rather than on the normal or transformed character of the parental cell lines of the hybrid cell populations.

Animals↗
PubMed1989

Rearrangement and diversification of immunoglobulin light-chain genes in lymphoid cells transformed by reticuloendotheliosis virus.

Avian lymphoid cells transformed by reticuloendotheliosis virus (REV-T) serve as a model to analyze the mechanism by which B-cell differentiation and antibody diversification occur in birds. Immunoglobulin light-chain gene rearrangements, diversification, and expression were analyzed in 72 independently derived REV-T-transformed cell lines. Lymphoid cells transformed as the result of expression of the v-rel oncogene were divided into two distinct groups based on light-chain gene rearrangements. The status of the light-chain gene loci in these REV-T-transformed cell lines was determined in part by the ages of the chickens whose spleen cells were transformed. In embryonic spleen cell lines transformed by the v-rel oncogene, rearrangements were not detected, even after prolonged culture in vitro, indicating that these cells are arrested in B-cell differentiation. REV-T transformants derived from spleens obtained from chickens 2 weeks old or older, however, had at least one light-chain allele rearranged. All of the cell lines analyzed which exhibited rearranged light-chain genes contained light-chain transcripts, and most of the REV-T-transformed cells which displayed light-chain rearrangements expressed immunoglobulin protein. REV-T, therefore, transforms B-lymphoid cells at phenotypically different stages of development. Many REV-T-transformed cells undergo immunoglobulin chain gene rearrangements during prolonged propagation in vitro. Most of the cell lines which rearrange their light-chain alleles also undergo diversification during cultivation in vitro. Light-chain diversification occurs during or after the rearrangement event.

Aging↗
PubMed1980

Consistent chromosome abnormalities associated with mouse bladder epithelial cell lines transformed in vitro.

Nine epithelial tumor cell lines that were derived from inbred C57BL/lcrf-at adult male mouse bladder and were transformed in vitro were cytogenetically analyzed. Most cell lines were near-diploid and showed only minor karyotypic deviations from normal. Tetraploid cell lines showed duplication of chromosome markers, which suggested that they arose originally as near-diploid cell lines with minor karyotypic changes. Chromosome abnormalities were consistent among different cell lines and involved chromosomes #6, #3, and #15. The Y-chromosome was frequently missing. Identical chromosome abnormalities were present in cell lines that arose in control, dimethyl sulfoxide-treated, or 7, 12-dimethylbenz[a]anthracene-treated cultures. The most frequent abnormality was was the presence of three copies (trisomy) of chromosome #6. Few structural chromosome abnormalities were detected, although a marker chromosome derived from chromosome #3 was present in several cell lines. Two cell lines had excesses of chromosome #15. These results suggest that excesses of individual chromosomes or parts of chromosomes, particularly chromosome #6, may be important in the expression of the malignant phenotype in mouse bladder epithelium.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Induction of syncytia by simian sarcoma virus type I (SSV-I/SSAV-I) in several human transformed cell lines.

Simian sarcoma virus type I (SSV-I/SSAV-I) induced syncytia formation in human cells derived from malignant tumors (KB, HEp-2 and HeLa cells) and human cells transformed by tumor viruses (RSa, RSb and KC cells) as well as rat XC cells. However, SSV-I/SSAV-I did not induce syncytia formation in human cells derived from normal embryos (WI-38, HEL and HEC). Syncytia-inducing activity of SSV-I/SSAV-I was neutralized by anti-SSV-I/SSAV-I serum, indicating that syncytia formation was SSV-I/SSAV-I mediated.

Cell Fusion↗
PubMed1994

Ornithine decarboxylase gene expression is aberrantly regulated via the cAMP signal transduction pathway in malignant H-ras transformed cell lines.

We have tested the hypothesis that H-ras transformed cells contain alterations in signal pathways important in controlling the expression of ornithine decarboxylase (ODC), the highly regulated rate-limiting activity in the biosynthesis of polyamines. Mouse 10T1/2 fibroblasts and a series of 10T1/2 H-ras transformed cell lines were treated with stimulators of cAMP synthesis (forskolin and cholera toxin), a biologically stable analogue of cAMP (8-bromo-cAMP), and an inhibitor of cAMP degradation (3-isobutyl-1-methylxanthine). Elevations in ODC gene expression were noted in H-ras transformed cells that were not observed in parental 10T1/2 fibroblasts. The forskolin-mediated effects were not detected with 1,9-dideoxyforskolin, a compound structurally related to forskolin, which does not activate adenyl cyclase. The effects observed with cholera toxin were not detected when cells were treated with the purified subunits of this compound, indicating that the toxin-induced effects were cAMP-specific. Actinomycin D treatment prior to forskolin exposure reduced the elevation observed in ODC gene expression indicating the involvement of the transcriptional process. Furthermore, we observed that cycloheximide treatment of malignant but not benign H-ras transformed cells significantly elevated ODC message level. Treatment of malignant cells with both cycloheximide and forskolin together resulted in a further additive elevation in ODC message, but a similar treatment of benign tumor cells reduced the forskolin-mediated increase in ODC message. In addition, treatment of H-ras transformed cells with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) led to an elevation in ODC mRNA levels not observed in parental 10T1/2 fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1990

Establishment of a SV40-transformed cell line from primary culture of rat dorsolateral prostatic epithelial cells.

A permanent cell line of the rat dorsolateral prostate epithelium was established after transformation of primary cultured cells with simian virus 40 (SV40). The established cells had SV40 T-antigen in their nuclei but lacked such typical characteristics of transformed cells as piled-up growth. They grew in a monolayer with an epithelial morphology, were stained with antikeratin antisera, and also retained an ability to form dome-like structure at a confluent state.

Animals↗
PubMed1993

Specificity of bischloroethylnitrosourea-induced mutation in a Chinese hamster ovary cell line transformed to express human O6-alkylguanine-DNA alkyltransferase.

The human O6-alkylguanine-DNA alkyltransferase complementary DNA was transfected into the alkyltransferase-deficient Chinese hamster ovary cell line, D422, in an effort to dissect the underlying mechanisms of bischloroethylnitrosourea (BCNU)-induced mutations. The alkyltransferase-transformed cell line exhibited 100-fold protection against BCNU-induced toxicity and an overall decrease in mutation frequency to 25% of that observed in the parental cell line at the hemizygous adenine phosphoribosyl transferase gene target. The frequency of the predominant mutation in the parental cell line, the G:C-->T:A transversion, was reduced from 16 x 10(-6) to 0.7 x 10(-6) in the O6-alkyltransferase-transformed cell line. Likewise, the G:C-->A:T transitions, the second most common BCNU-induced mutation in the parental cell line, was reduced in frequency from 5.2 x 10(-6) to 0.9 x 10(-6) in the alkyltransferase-transformed Chinese hamster ovary cells. These findings suggest that both the G:C-->T:A transversions and G:C-->A:T transitions were O6-alkylguanine-mediated mutations. In the alkyltransferase-transformed Chinese hamster ovary cell line, T:A-->G:C transversions, comprising 45% (23 of 51) of the recovered mutations, emerged as the most common base substitution. In summation, in the absence of alkyltransferase-dependent DNA repair, mutations resulting from O6-alkylation of guanine underlie both the cytotoxic and mutagenic activity of BCNU. In cells expressing high levels of alkyltransferase activity, the cytotoxic and mutagenic actions of BCNU are greatly reduced and mutations resulting from A:T base pair modifications appear to be the major genotoxic lesions induced by the drug.

Animals↗
PubMed2007

High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines.

The E6 oncoproteins of high-risk HPV types 16 and 18 are involved in the development of cervical cancer. Besides its determinant role in carcinogenic progression, HPV E6 oncoprotein has also been instrumental in elucidating fundamental aspects of p53 function and its ubiquitin-proteasome degradation, with counterpart activities in various DNA tumor viruses. Establishing the conformational state and cellular distribution unequivocally for the endogenous protein in HPV-transformed cell lines derived from carcinomas is essential for understanding the underlying mechanism. Recombinant E6 from high-risk strains 16 and 18 folds into soluble oligomers of approximately 1.2 MDa, which are thermostable and display cooperative loss of tertiary and secondary structure upon chemical denaturation. Antibodies raised against these assemblies locate E6 evenly distributed in the cells. By depleting the polyclonal serum by immunoblocking with monomeric E6, the nuclei of Hela and CaSki cells become completely devoid of label, indicating that monomeric species are mainly localized in the nucleus and that both monomers and oligomers share epitopes. The monomeric species promote degradation of p53 by the proteasome, which correlates with the nuclear localization we describe. In contrast, the oligomeric E6 does not promote p53 degradation, in agreement with its cytoplasmic localization inferred from the immunoneutralization experiments. Our results indicate that the cytoplasmic species contain conformational epitopes that may arise from yet undefined homo or hetero-oligomers, but its localization otherwise agrees with that of the other group of major E6 targets, those involving PDZ binding domains, which requires further investigation.

Base Sequence↗
PubMed1986

Recombinant tumor necrosis factor: species specificity for a variety of human and murine transformed cell lines.

Tumor necrosis factor (TNF) exhibits cytotoxic or cytostatic activity on a wide range of animal and human transformed cell lines. Using pure, recombinant human and mouse TNF, we examined the degree of species specificity of the in vitro TNF activity on a variety of human and murine transformed cell lines. This species specificity was studied for the TNF activity alone or in synergism with IFN-gamma. Recombinant human and mouse TNF behave remarkably similarly regarding the in vitro cytolytic/cytostatic activity. However, a certain degree of species-specific preference could be revealed as human cell lines needed a higher concentration of recombinant mouse TNF than of recombinant human TNF to attain a similar effect, while on mouse cells the reverse was true. Also, synergism with IFN-gamma seemed more effective when the target cell was treated with homologous TNF.

Animals↗