Hepatic peroxisome proliferators induce morphologic transformation of Syrian hamster embryo cells, but not peroxisomal beta oxidation.
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2,4,5-Trichlorophenoxyacetic Acid↗
Biomedical subjects
T Sanner
Publications and source records attributed to T Sanner.
Role of catalase and oxidative stress in hepatic peroxisome proliferator-induced morphological transformation of Syrian hamster embryo cells.
Several hepatic peroxisome proliferators (HHPs) such as di(2-ethylhexyl)phthalate (DEHP), mono(2-ethylhexyl)-phthalate, clofibrate and tiadenol, induce morphological transformation of Syrian hamster embryo (SHE) cells in vitro. According to one hypothesis, the hepatocarcinogenic effect of HPPs is caused by an oxidative stress due to increased H2O2-production from the strongly induced peroxisomal beta-oxidation of fatty acids. Thus, increased transformation frequencies by HPPs should be obtained when catalase was inhibited by 3-amino-1,2,4-triazole (amitrole). However, co-exposure to HPPs and amitrole did not enhance the transformation frequencies for any of the HPPs. The sensitivity of SHE cells for oxidative agents was studied by using menadione and H2O2. Menadione only induced transformation at a toxic concentration, while H2O2 induced transformation at non-toxic concentrations. To study the generation of oxidative radicals in SHE cells, electron spin resonance was employed. No oxidative radical formation was detected in tiadenol- or DEHP-exposed SHE cells. When menadione or H2O2 were added during the measurements, oxidative radicals were found. A transmission electron microscopic study showed a small number of peroxisomes, and did not reveal any increase in the number of peroxisomes in clofibrate-treated SHE cells.
Amitrole↗
The non-phorbol ester tumor promoter okadaic acid does not promote morphological transformation or inhibit junctional communication in hamster embryo cells.
Okadaic acid is a potent non-phorbol ester mouse skin tumor promoter. Unlike the phorbol ester tumor promoters, okadaic acid is unable to promote the induction of morphological transformation in Syrian hamster embryo cell colonies. On the contrary, okadaic acid seems to counteract the effect of phorbol esters on transformation. Also unlike phorbol ester tumor promoters, okadaic acid does not inhibit intercellular communication, neither in primary hamster embryo cells, nor in the phorbol ester sensitive cell line BPNi. Furthermore, okadaic acid has no effect on the reoccurrence of communication following removal of 12-O-tetradecanoylphorbol-13-acetate.
Animals↗
Effects of hepatic peroxisome proliferators and 12-O-tetradecanoyl phorbol-13-acetate on catalase and other enzyme activities of embryonic cells in vitro.
The effects of the hepatic peroxisome proliferators (HPPs) clofibrate, di-(2-ethylhexyl)-phthalate (DEHP), mono-(2-ethylhexyl)phthalate (MEHP) and 2,4-dichlorophenoxy acetic acid (2,4-D) on the activities of some peroxisome-associated enzymes and marker enzymes for other organelles, have been studied in primary Syrian hamster embryo (SHE) cells and Wistar rat embryo (WRE) cells. The majority of the cells are fibroblast-like. 12-O-Tetradecanoyl phorbol-13-acetate (TPA) was included as it has been suggested that it may act as a peroxisome proliferator. The specific activities of catalase, fatty acyl-CoA oxidase (FAO) and peroxisomal beta-oxidation were approximately 100-fold lower in the embryonic cells than in rat hepatocytes. Other peroxisome-associated oxidases were not detected. The dihydroxyacetone-phosphate acyltransferase (DHAPAT) activity was comparable to that in rat liver. Marker enzymes for other organelles had specific activities comparable to rat hepatocytes. Catalase was shown by digitonin titration to be contained in a peroxisome-like compartment in both SHE and WRE cells. Clofibrate, DEHP and MEHP increased the catalase activity, which might suggest peroxisome proliferation. However, the findings that FAO and peroxisomal beta-oxidation did not increase or only very slightly, argue against peroxisome proliferation. 2,4-D and TPA induced no or only a very slight increase in the catalase activity.
2,4-Dichlorophenoxyacetic Acid↗
Morphological transformation and catalase activity of Syrian hamster embryo cells treated with hepatic peroxisome proliferators, TPA and nickel sulphate.
The abilities of the hepatic peroxisome proliferators (HPPs) clofibrate, di(2-ethylhexyl)phthalate (DEHP), mono(2-ethylhexyl)-phthalate (MEHP), 2,4-dichlorophenoxy acetic acid (2,4-D), 2,4,5-trichlorophenoxy acetic acid (2,4,5-T) and tiadenol to induce morphological transformation and to increase the catalase activity of Syrian hamster embryo (SHE) cells were studied. DEHP, MEHP, clofibrate and tiadenol induced morphological transformation of SHE cells and increased the catalase activity. DEHP was more potent than clofibrate and tiadenol in both inducing catalase and morphological transformation, while MEHP seemed more potent than DEHP in inducing catalase, but not morphological transformation, 2,4,5-T and 2,4-D did not induce morphological transformation, but 2,4,5-T was more potent than clofibrate in increasing the catalase activity. These results show that several HPPs induce morphological transformation of SHE cells and an increase in the catalase activity. There is, however, no direct connection between these two parameters, as seen from the results of 2,4,5-T. The tumor promoter TPA, and the metal salt nickel sulphate, induced morphological transformation of SHE cells without any appreciable increase in the catalase activity. These results further corroborate the dissociation between induction of morphological transformation and the increase in catalase activity.
2,4,5-Trichlorophenoxyacetic Acid↗
Vanadium compounds promote the induction of morphological transformation of hamster embryo cells with no effect on gap junctional cell communication.
Vanadium compounds were found to promote the induction of morphological transformation of hamster embryo cells. Exposure of the cells to Na-O-vanadate, vanadin (V) oxide or vanadin (IV) oxide sulfate following pre-exposure to a low concentration of benzo[a]pyrene, potentiated the induction of transformed colonies similar to 12-O-tetradecanoylphorbol-13-acetate. Unlike this phorbol ester, vanadium compounds did not inhibit intercellular communication, or active protein kinase C. Nor did vanadate influence the reoccurrence of communication after removal of a communication blocking phorbol ester. On the other hand, vanadate showed strong synergism with the phorbol ester on induction of transformed morphology in the phorbol ester sensitive cell line BPNi. This suggests that vanadium and tumor promoting phorbol esters mediate their effect on the induction of morphological transformation of hamster embryo cells through different mechanisms.
Animals↗
Effects of dinitrotoluenes on morphological cell transformation and intercellular communication in Syrian hamster embryo cells.
The effects of four isomers of dinitrotoluene (DNT) and technical DNT (a mixture of DNT isomers and other compounds, with 2,4-DNT as the major constituent) were studied in two short-term in vitro assays. None of the isomers or technical DNT induced an increase in morphological transformation of Syrian hamster embryo (SHE) cells. Four DNT metabolites (2,4-diaminotoluene, 2-amino-4-nitrotoluene, 2-amino-6-nitrotoluene, and 2,4-dinitobenzoic acid), representing different stages in reduction or oxidation of DNT isomers, were also negative for induction of morphological transformation. The DNT isomers were tested in an intercellular communication assay based on dye transfer. 2,4-DNT, 2,6-DNT, and technical DNT inhibited intercellular communication in the SHE cell line BPNi at toxic concentrations. This may be reminiscent of in vivo data showing promoting activity of these compound. 2,3-DNT and 3,4-DNT did not inhibit communication.
Animals↗
[Indoor radon exposure and risk of lung cancer].
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Air Pollutants↗
Role of T-lymphocytes in production of a cancer-associated protein factor in serum from lung cancer patients.
Oligoclonal T-cells have been generated by sensitization of peripheral blood mononuclear cells from lung cancer patients to a lung cancer tumor-associated antigen (TAA). A factor similar to the antigen-specific glycoprotein factor in the serum of these cancer patients was found in the supernatant of the oligoclonal T-cells. The factor from the T-cell supernatant had specificity for lung cancer TAA and induced stimulation of normal lymphocytes of the CD8 phenotype when mixed with lung cancer TAA. Furthermore, the factor blocked the ability of lymphocytes from lung cancer patients to recognize lung cancer TAA. Both the factor from lung cancer serum and from the oligoclonal T-cells were absorbed on a lung cancer-associated antigen-coupled immunosorbent column. On FPLC-gel filtration the desorbed fractions from the immunosorbent column from both sources showed activity in the same molecular weight range, 70-90 kD. Heteroantisera raised against the factor from serum and against the factor from the oligoclonal T-cell supernatant bound about the same portion of lymphocytes from lung cancer patients as measured by immunofluorescence, while only a minor fraction of cells from patients with unrelated cancers and from healthy persons were labelled on incubation with the antisera. These results support the hypothesis that an antigen-specific factor found in serum of cancer patients is produced by antigen-stimulated T-cells, possibly of the CD8 phenotype. This putative antigen-specific suppressor factor and the tumor antigen-reactive lymphocytes of the patient seem to share similar idiotopes.
Antigens, Neoplasm↗
Morphological transformation of Syrian hamster embryo cells induced by mineral fibres and the alleged enhancement of benzo[a]pyrene.
The ability of different mineral fibres to induce morphological transformation of Syrian hamster embryo cells has been studied. Increased transformation frequencies were obtained in the presence of chrysotile, crocidolite, amosite, anthophyllite and the glass fibres (GF) 100, while no significant increase in transformation frequency was observed with GF 110 and TiO2. Chrysotile was the most potent of the fibres tested. GF 100 was more potent than crocidolite, amosite and anthophyllite. By comparing transformation frequency and toxicity, it could be concluded that induction of transformation is not caused by unspecific cytotoxic effects. In contrast to some earlier studies, no synergistic effect was observed between benzo[a]pyrene (BaP) and asbestos fibres. Adsorption of BaP to crocidolite fibres had no effect on the transformation frequency. Moreover, crocidolite was not able to promote the transformation of cells pre-exposed to BaP. Electron microscopy studies showed that the fibres were rapidly phagocytosed. Blebs were often formed on the cell surface and were most pronounced after crocidolite exposure. The blebs did not seem to be associated with the areas of physical interaction between the cells and the fibres, but were distributed throughout the cell surface.
Animals↗
Humoral leukocyte adherence inhibition response in patients with oral cancer.
Antitumor immunity was assessed in a group of 10 patients suffering from squamous cell carcinoma of the oral cavity using the humoral leukocyte adherence inhibition assay (H-LAI). A tumor extract from a person with cancer of the tongue was used as antigen. Sera from five patients with carcinoma of the tongue were all positive in the test. Of the other five patients, three had cancer of the lips while in two patients the type was unspecified. All patients except one with cancer of the lips gave a positive response in the test. Thus, of the 10 patients with carcinoma of the oral cavity, nine responded. Among nine controls, one person gave a positive response.
Antigens, Neoplasm↗
[Cancer risk with the use of smokeless tobacco (snuff and chewable tobacco)].
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Dental Care↗
Cell-populations involved in the humoral leukocyte adherence inhibition reaction. The T8-suppressor/cytotoxic cells are both effectors and responders.
In an attempt to identify the cell subpopulation involved in the humoral leukocyte adherence inhibition (H-LAI) reaction, mononuclear leukocytes were fractionated and the response with the different cell populations was measured in the H-LAI assay using sera from lung cancer patients and a lung cancer associated antigen. The monocytes were found to exhibit a suppressive effect on the H-LAI response. The B-lymphocytes seemed not to take an active part in the reaction. Depletion of the T-lymphocytes abolished the reaction. Subsequent studies on the T-lymphocyte subpopulations revealed that removal of the T4-cells had little effect while removal of the T8-cells resulted in complete abrogation of the H-LAI response. Direct blocking by monoclonal antibodies against the T4 and T8 surface determinants gave additional support for the T8-cell dependency of the H-LAI assay. The cells that specifically were induced to loose adherence in the H-LAI assay upon incubation with serum from a lung cancer patient and lung cancer associated antigen were also analyzed. Compared to the total mononuclear leukocyte population, the relative content of monocytes and B-cells were lower in the non-adherent population. An increase was found in the relative number of T-cells. While the relative number of T4-cells decreased, the content of T8-cells was significantly increased. Furthermore, a direct correlation was found between the loss of adherence of the T8-subpopulation and the index of the H-LAI response. The present study indicates the T8-subpopulation of the T-lymphocytes to be involved both in the effector and responder side of the H-LAI reaction and gives implications for an immunological reaction behind the response of the H-LAI assay.
Antibodies, Monoclonal↗
Cell transformation and promoter activity of insulation oils in the Syrian hamster embryo cell and in the C3H/10T1/2 mouse embryo fibroblast test systems.
The ability of mineral-oil-based and synthetic cable insulating fluids to transform and promote transformation of mammalian cells in vitro have been studied. In experiments with the Syrian hamster embryo cell transformation assay, it was found that C15-C18 alkylbenzenes were the most potent inducers of transformation, followed by low-viscosity and residual mineral oils. No activity and low cytotoxicity were found for a low-viscosity polyisobutylene-based oil. In the two-stage transformation assay of C3H/10T1/2 cells, promoter activity was obtained with all fluids tested. A blend of residual and low-viscosity mineral oils showed the highest activity. This oil possessed a low cytotoxicity and was tested at a relatively high concentration. The alkylbenzenes were more potent than the polyisobutylene-based fluid. The alkylbenzenes were also found to possess initiating activity in the two-stage assay, when 12-O-tetradecanoylphorbol 13-acetate (TPA) was used as promoter. All the fluids showed low potency compared to benzo[a]pyrene and the tumor promoter TPA.
Animals↗
Initiation of in vitro cell transformation by formaldehyde and acetaldehyde as measured by attachment-independent survival of cells in aggregates.
The ability of formaldehyde and acetaldehyde to initiate transformation of a rat kidney cell line has been studied using a newly developed two-stage in vitro cell transformation assay. The assay is based on measurements of attachment-independent survival of cells in aggregates. Short treatment with non-cytotoxic doses of formaldehyde and acetaldehyde did not affect survival of the cells in the aggregate assay system. However, when the aldehyde treatment was followed by exposure of the cells to the tumor promoters TPA and PDD, a considerable increase in the number of viable cells was observed. On a molar basis, formaldehyde was about 100 times more potent than acetaldehyde in initiation of cell transformation. The data showed that cells derived from aggregates of cultures treated with formaldehyde or acetaldehyde followed by exposure to TPA possessed a considerably higher ability to form colonies in soft agar than untreated control cells.
Acetaldehyde↗
Detection of ovarian cancer by the humoral leukocyte adherence inhibition test using a purified tumor-associated antigen.
The defined, purified ovarian cancer-associated antigen, NB/70K, was used as tumor antigen in the humoral leukocyte adherence inhibition (H-LAI) assay. Bell-shaped dose-response relationships were obtained with increasing concentrations of NB/70K and constant serum concentration from ovarian cancer patients. The concentrations of NB/70K used in this study were 100-250 times less than what had been used in previous H-LAI studies with crude antigen extracts. The response rate of ovarian cancer patients was greatly influenced by the stage of the disease. Thus 75% (6/8) of the patients with disease restricted to the pelvis (stages I and II) reacted while only 20% (5/24) of the patients with more advanced stages (stages III and IV) gave response. Of patients with other gynecological cancers, 17% (1/6) were positive and only 8% (1/13) of patients with other malignant diseases reacted. One of the 11 controls (9%) was found to give positive response. The importance of the present investigation was the finding that a defined, purified, cancer-associated antigen elicited reactivity in the H-LAI assay and that a high sensitivity for detection of early stages of ovarian cancer was obtained with this antigen. The results suggest that TAAs involved in immune recognition of cancer can be identified by the H-LAI assay.
Antigens, Neoplasm↗
Caffeine and other phosphodiesterase inhibitors are potent inhibitors of the promotional effect of TPA on morphological transformation of hamster embryo cells.
The phosphodiesterase inhibitors caffeine, theophylline, aminophylline and isobutyl-methylxanthine (IBMX) were found to inhibit induction of morphologically transformed hamster embryo cell colonies by sequential exposure to benzo[a]pyrene (BaP) and the tumor promoter TPA. Almost complete inhibition of cell transformation was observed when 50 micrograms/ml theophylline, aminophylline, IBMX, or 200 micrograms/ml caffeine was present together with the tumor promoter. The compounds had no effect on the transformation frequency when present together with the initiator, BaP, in the first exposure period. Substances that stimulate the adenylate cyclase and the addition of exogenous dibutyryl-cAMP had similar inhibitory effects.
Adenylyl Cyclases↗
Inhibition of intercellular communication and enhancement of morphological transformation of Syrian hamster embryo cells by TPA. Use of TPA-sensitive and TPA-resistant cell lines.
The possible role of blocked intercellular communication in the process of cell transformation has been studied with Syrian hamster embryo cell lines which are sensitive or resistant to TPA-induced enhancement of morphological transformation. Both the TPA-sensitive (BPNi) and the TPA-resistant (83-106 and 74-100) cell lines showed gap-junctional communication when measured by a dye-transfer method. However, TPA inhibited the communication only in TPA-sensitive cells, and not in TPA-resistant cells. These results are consistent with the idea that blocked intercellular communication is involved in a late stage of cell transformation and/or expression of the transformed phenotype.
Animals↗