Biodegradation of hazardous wastes.
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Azo Compounds↗
Biomedical subjects
W A Suk
Publications and source records attributed to W A Suk.
Potential carcinogenicity of aza-aromatic hydrocarbons: azabenz(a)anthracenes.
The potential carcinogenicity of 3 azabenz(a)anthracenes was determined in vitro. The 3 compounds tested were 1-, 2-, and 9-azabenz(a)anthracene. The initial assay was chemical carcinogen-induced enhancement of anchorage-independent survival of Rauscher leukemia virus-infected Fischer rat embryo cells, 2FR(4)50 (2FR4). Cells treated with 2- and 9-azabenz(a)anthracene showed dose-dependent increased survival. After continued subculturing, the surviving cells from 2- and 9-azabenz(a)anthracene-treated cultures displayed morphological transformation and ability to grow in semi-solid medium. Mock-treated controls and I-azabenz(a)anthracene-treated cultures did not show either of these properties. These data suggest that certain azabenz(a)anthracenes are potential carcinogens.
4-Nitroquinoline-1-oxide↗
Induction of endogenous xenotropic retrovirus expression by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate.
The tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) was examined for its ability to induce endogenous retrovirus from a high-passage clone of Kirsten sarcoma virus-transformed Balb/c (K-Balb) mouse cells. TPA activated virus in a concentration-dependent manner (0.0016 to 4.0 microM). Exposure to 1mM actinomycin D inhibited virus induction, suggesting that cellular RNA synthesis is required de novo by this inducer. A broad-spectrum neutralizing antibody to murine type C virus, gp70, was shown to neutralize the infectivity of the induced virus. The activated virus had the host range of the xenotropic Balb virus:2, and after removal of the inducer, the activated state decayed rapidly. TPA stimulated DNA, RNA, and protein synthesis in K-Balb cells, indicating that the mechanism of induction may be different from that of previously identified virus inducers. The effects observed using the well-defined K-Balb system offer an opportunity to study the modulation of retrovirus gene expression by TPA.
Animals↗
Chemical enhancement of survival in aggregation of retrovirus-infected rat cells: an interlaboratory comparison.
This study provides a comparative evaluation among three independent laboratories of the responses to 16 chemicals in the retrovirus (Rauscher leukemia) infected Fischer rat embryo (RIFRE) cell-survival-in-aggregation assay. When suspended in liquid media above an agar base, control cells showed a rapid decline in cell survival, whereas cells that had previously been treated with chemical carcinogen survive in suspension longer than control cells. The endpoint, survival in aggregation, is measured by counting viable cells dissociated from aggregates in suspension for 4 days. By modifying previously reported procedures, we have improved the system so that a clear differential (positive or negative) response is achieved by cells treated with either a known carcinogen or known noncarcinogen. Using procedures designed to minimize assay variability, replicate assays were performed and the data analyzed for inter- and intralaboratory concordance. The RIFRE cell-survival-in-aggregation assay demonstrated a high degree of interlaboratory reproducibility in assessing the overall positive or negative responses of known carcinogens and noncarcinogens, and good qualitative reproducibility in assessing compounds tested under code. The assay could discriminate between known carcinogens and noncarcinogens. All chemicals were tested without the addition of a metabolic activation system. Cells exhibiting carcinogen-induced enhancement of survival in aggregation, when plated back onto a solid substrate and carried in culture, subsequently expressed transformation-associated changes in their cellular morphology, growth in semisolid media, and tumorigenicity in nude mice. These results indicate that retrovirus-infected Fischer rat embryo cells detect a carcinogen-mediated early event that progresses to neoplastic phenotypes. Survival in aggregation appears to require the presence of the exogenous retrovirus, since uninfected cells did not show a differential survival response when carcinogen-treated, noncarcinogen-treated, or control cells were compared. This system provides a reproducible method of detecting carcinogenic chemicals based on their ability to induce enhanced survival in aggregation of treated cells.
Animals↗
Interaction between nontransforming retroviruses and chemicals in cells in vitro: association with progression to neoplastic phenotypes.
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Animals↗
Enhancement of endogenous xenotropic murine retrovirus expression by tuftsin.
The exposure of a high-passage clone of Kirsten sarcoma virus transformed Balb/c (K-Balb) mouse cells to tuftsin (Thr-Lys-Pro-Arg) enhanced the expression of endogenous xenotropic retrovirus. The tetrapeptide increased the expression of virus that was infectious for rat, but not mouse, cells in a concentration-dependent fashion (0.001-1000 micrograms/ml). Increased virus expression could be achieved during short-term incubations (3-4 hr), with maximum enhancement occurring over longer time periods (16-18 hr). The enhancement of virus expression by tuftsin was proportional to the spontaneous release of virus. The infectivity of the enhanced virus was neutralized by goat anti-RLV gp 70 serum. Actinomycin D inhibited the induction of virus, suggesting that enhanced expression required de novo RNA synthesis. Tuftsin stimulated DNA, RNA, and protein synthesis in K-Balb cells during 16-hr incubations. Increased cellular proliferation was also seen at various time periods. The effects observed using K-Balb cells offer an opportunity to study the modulation of gene expression by tuftsin in a fibroblast culture system.
Animals↗
Inhibition of endogenous murine retrovirus expression by L-beta-3,4-dihydroxyphenylalanine (L-dopa) methyl ester.
Induction of endogenous xenotropic type-C virus from Kirsten sarcoma-virus-transformed BALB/c (K-BALB) mouse cells was inhibited by short-term exposure to L-beta-3,4-dihydroxyphenylalanine (L-dopa) methyl ester. Partially synchronized cells cultured for 1-4 h with 0.8-1.6 mM L-dopa methyl ester and subsequently induced with 5-iododeoxyuridine (IdUrd), cycloheximide and histidinol showed inhibition of virus activation. Incorporation of thymidine, uridine and leucine was measured at the end of the drug treatment and during the subsequent induction period. L-dopa methyl ester had a pronounced effect on DNA synthesis, reducing it by more than 85% during a 4-h incubation period, whereas RNA and protein synthesis remained largely unaffected. Removal of the drug and replacement with fresh medium did not reverse DNA synthesis or virus activation during the subsequent induction interval. L-dopa methyl ester was also shown to potentially function as an analogue of tyrosine in this cell system. These results suggest that inhibition of virus induction may be caused by inhibiting the normal progressing of cells through the S phase of the cell cycle.
Animals↗
Juvenile hormones inhibit murine cell cycle progression and expression of type C viruses.
Juvenile hormones (JH), congeners of retinoic acid, were examined for their capacity to inhibit cell cycle progression and chemically induced expression of endogenous xenotropic retrovirus in Kirsten sarcoma virus-transformed BALB (K-BALB) mouse cells. JHI, II, and III were found to inhibit induction of virus by 5-iododeoxyuridine (IUdR) and histidinol (Hdl) in a concentration-dependent fashion. Some inhibition of macromolecular synthesis was observed upon culture of the cells with JH; the most affected was RNA synthesis, which was reduced 27 to 40% within 4 h by the juvenoids. Epoxide hydrase (EH) activity, as determined by high-pressure liquid chromatography (HPLC), was present in amounts sufficient for the cells to convert the hormones metabolically to an ultimate form. A contact-inhibited K-BALB variant was synchronized by mitotic arrest and the cell cycle-specific effect of JHIII on virus induction during S phase was studied. JHIII added during G1 phase, and followed by induction, inhibited virus expression 95 and 76% by IUdR and Hdl, respectively. Induction was inhibited only 35% when JHIII was added during S phase concomitantly with the inducers and no inhibition was observed when JHIII was added during G2 phase followed by the inducers. JHIII added to synchronous cells in G1 phase inhibited progression of cells into S phase and the onset of DNA synthesis. The results indicate that mouse fibroblasts have a juvenile hormone-sensitive restriction point in G1 phase that might relate to the effects these hormones have on cell replication and differentiation.
Animals↗
Increased expression of endogenous xenotropic murine retrovirus by treatment with the tetrapeptides, tuftsin and kentsin.
Enhancement of endogenous xenotropic virus expression has been found upon treatment with tetrapeptides of a high-passage clone of Balb/c (K-Balb) mouse cells transformed with Kirsten sarcoma virus. Tuftsin (Thr-Lys-Pro-Arg) and kentsin (Thr-Pro-Arg-Lys) increased the expression of virus that was infectious for rat, but not mouse, cells in a concentration-dependent fashion. The enhancement of virus expression by the tetrapeptides was proportional to the spontaneous release of virus. The infectivity of the enhanced virus was neutralized by goat anti-RLV gp70 serum. Actinomycin D inhibited the induction of virus, suggesting that enhanced expression required de novo RNA synthesis. The effects observed using K-Balb cells offer an opportunity to study the many biological effects of these peptides in a fibroblast culture system.
Animals↗
Cell cycle-specific inhibition by retinoic acid of xenotropic murine retrovirus expression.
Several retinoids were examined for their capacity to block chemically induced expression of endogenous xenotropic retrovirus from Kirsten sarcoma virus-transformed BALB/c mouse cells. Retinoic acid (RA) was found to inhibit induction of virus by 5-iododeoxyuridine, cycloheximide, and histidinol; inhibition was concentration (10(-4) to 10(-6) M) and time dependent (1 to 7 hr) and not a consequence of cytotoxicity. Following a 6-hr treatment with 10(-4) M RA, [3H]thymidine and [3H]uridine incorporation into total cellular DNA and RNA was reduced 37 and 63%, respectively. Heteronuclear RNA synthesis was reduced 36 and 7% within 4 hr by 10(-4) and 10(-5) M RA, respectively, indicating that inhibition was not the result of a general transcriptional block. Using synchronized cells, it was found that 5 X 10(-5) M RA added in G1 phase and followed by cycloheximide or 5-iododeoxyuridine induction inhibited virus expression 60 and 84%, respectively. Little or no inhibition was observed when RA was added during S phase with the inducers or during G2 phase followed by inducers. Cells synchronized by mitotic arrest showed a RA-mediated restriction point in early-to-mid-G1 phase as indicated by a delay in the onset of DNA synthesis and an inhibition of virus induction during S phase. The results show the presence in Kirsten sarcoma virus-transformed BALB/c cells of a RA-sensitive G1 restriction point for cell progression and suggest that inhibition of retrovirus activation may be related to an extended G1 phase.
Animals↗
Cell cycle-specific enhancement of type C virus activation by sodium n-butyrate.
The effect of sodium n-butyrate on chemical induction of xenotropic virus from synchronized Kirsten sarcoma virus-transformed BALB mouse cells was examined. When added during the last part of the G1 phase, n-butyrate produced a large increase in cycloheximide induction during S phase. Under similar conditions, activation by 5-iododeoxyuridine was inhibited. When added with cycloheximide during the S phase, n-butyrate inhibited activation of virus. Studies with synchronized cultures showed that n-butyrate delayed the onset of DNA synthesis, characteristic of the S phase, and inhibited histone deacetylation in log-phase cells. The effects produced by n-butyrate could, therefore, be the result of lengthening the G1 phase of the cell cycle or a modification of histones affecting transcription during virus activation.
Animals↗
Effects of protease inhibitors on chemical induction of type C virus.
A role for proteolysis during chemical induction of endogenous xenotropic Type C virus from Kirsten sarcoma virus-transformed mouse cells was examined. Two distinct classes of protease inhibitors, the trypsin inhibitor, alpha-N-tosyl-L-lysine chloromethyl ketone, and two naturally occurring oligopeptide inhibitors, antipain and leupeptin, were found to inhibit induction of virus by cycloheximide and histidinol. Virus activation by 5-iododeoxyuridine was inhibited to a lesser degree. During the time cells were exposed to these compounds, there was little inhibition of [3H]uridine incorporation into total cellular RNA or polyadenylic acid cytoplasmic messenger RNA, suggesting that inhibition of proteolysis, and not RNA transcription, was responsible for blocking virus induction.
Animals↗
Activation of endogenous type C virus by amino acid alcohols.
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Amino Alcohols↗
In vitro and in vivo indications of the carcinogenicity and toxicity of food dyes.
Eight food dyes or commercial color mixtures certified for use in the United States were tested for their ability to transform in vitro a serial line of Fischer rat embryo cells previously reported to be a sensitive indicator of chemicals having carcinogenic potential. Malignant cell transformation was induced by a commercial mixture (G2024) of two of these dyes (Blue 1 and Yellow 5) and by Blue 2, Green 3 (one of two experiments) and Red 4. Food dyes Blue 1, Red 3, Yellow 5 and Yellow 6 did not induce cell transformation. One to 1.5 mg of each dye was injected into suckling LVG or Graffi hamsters which were monitored for tumor induction and/or death over a 330-day period. None of the non-transforming dyes (Blue 1, Red 3, Yellow 5, Yellow 6) or Green 3 induced a significant increase in tumor (mostly lymphoma) incidence or animal mortality. Three of the transforming dyes (Blue 2, Green 2024, Red 4) did increase tumor incidence and/or mortality in at least one strain of hamster. We conclude the the in vitro assay suggested that certain food dyes were carcinogens and that in vivo studies in hamsters supported this interpretation.
Animals↗
Chemical transformation of rat cells infected with xenotropic type-C RNA virus and its suppression by virus-specific antiserum.
Fischer rat embryo cells infected with xenotropic mouse type-C RNA viruses isolated from either NIH Swiss mice or C57L inbred mice were transformed by 4-nitroquinoline oxide or 3-methylcholanthrene under conditions in which neither treatment alone sufficed to induce transformation. Transformation was dependent on the presence of actively growing virus at the time of chemical treatment. Specific antibody to xenotropic virus neutralized the virus and inhibited malignant transformation by 3-methylcholanthrene.
Animals↗
Geldanamycin inhibition of 3-methylcholanthrene-induced rat embryo cell transformation.
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Anti-Bacterial Agents↗
Transforming potential of the anticancer drug adriamycin.
A Fischer rat embryo cell system in vitro, which had been shown to be highly accurate in identifying chemical carcinogens and to have application in the study of chemicals having anticancer properties, was used to study the anticancer drug adriamycin. At a nontoxic dose adriamycin not only did not protect the cells from transformation by the carcinogen 3-methylcholanthrene, but was found in two separate experiments to act on its own as a transforming agent.
Animals↗
Type-C RNA viruses of the NIH nude mouse.
Several types of tumors from various species were propagated in NIH athymic nude mice. Subsequently, cell lines were established from the tumors and examined for evidence of type-C virus activity. Hybrid mice (NIH Swiss and BALB/c) harbored murine type-C viruses of three categories: N-tropic, B-tropic and X-tropic.
Animals↗