MUTAGENIC EVALUATION OF 1,1,2,3-TETRACHLORO-2- PROPENE, A CONTAMINANT IN PULP MILL EFFLUENTS, USING A BATTERY OF IN VITRO MAMMALIAN AND MICROBIAL TESTS

1981 ◽  
Vol 23 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Jennifer A. Ellenton ◽  
George R. Douglas ◽  
Earle R. Nestmann

The mutagenicity of 1,1,2,3-tetrachloro-2-propene (TCP), a component of chlorinated pulp mill effluents, was investigated with a battery of in vitro mammalian and microbial assays. In fluctuation tests, TCP showed potent mutagenic activity with Salmonella typhimurium strain TA1535 but only very weak activity with Escherichia coli WP2. In Chinese hamster ovary (CHO) cells, TCP without metabolic activation induced chromosome aberrations. This activity was enhanced by the addition of Aroclor 1254-induced rat liver preparation (S9). Endoreduplication was also induced by TCP in the presence of S9. Without activation, TCP caused an increase in the number of sister chromatid exchanges (SCEs), however this increase was eliminated by S9. TCP did not cause DNA damage in CHO cells as measured by alkaline sucrose gradient sedimentation either with or without metabolic activation.

1992 ◽  
Vol 8 (6) ◽  
pp. 369-376 ◽  
Author(s):  
David H. Blakey ◽  
Earle R. Nestmann ◽  
Janet M. Bayley ◽  
K. Laurie Maus ◽  
George R. Douglas

Toluenesulfonhydrazide (TSH) is a high volume production chemical for which there is relatively little toxicological data. In this study, the mutagenic activity of TSH was determined in the Salmonella/mammalian microsome assay and the in vitro chromosomal aberration assay using Chinese hamster ovary cells. TSH induced gene mutations both with and without metabolic activation in the Salmonella/mammalian microsome assay but that it did not induce chromosomal aberrations in Chinese hamster ovary cells. The results of this study indicate that TSH is an in vitro mutagen and should be assessed for in vivo mutagenicity.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Andrea dos Santos Dantas ◽  
Luiz Carlos Klein-Júnior ◽  
Miriana S. Machado ◽  
Temenouga N. Guecheva ◽  
Luciana D. dos Santos ◽  
...  

The present study aimed to investigate thein vitromutagenic activity ofOriganum majoranaessential oil. The most abundant compounds identified by GC-MS wereγ-terpinene (25.73%),α-terpinene (17.35%), terpinen-4-ol (17.24%), and sabinene (10.8%). Mutagenicity was evaluated by theSalmonella/microsome test using the preincubation procedure on TA98, TA97a, TA100, TA102, and TA1535Salmonella typhimuriumstrains, in the absence or in the presence of metabolic activation. Cytotoxicity was detected at concentrations higher than 0.04 μL/plate in the absence of S9 mix and higher than 0.08 μL/plate in the presence of S9 mix and no gene mutation increase was observed. For thein vitromammalian cell micronucleus test, V79 Chinese hamster lung fibroblasts were used. Cytotoxicity was only observed at concentrations higher than or equal to 0.05 μg/mL. Moreover, when tested in noncytotoxic concentrations,O. majoranaessential oil was not able to induce chromosome mutation. The results from this study therefore suggest thatO. majoranaessential oil is not mutagenic at the concentrations tested in theSalmonella/microsome and micronucleus assays.


2004 ◽  
Vol 23 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Shiv Kumar Agarwal ◽  
Upendra Bhatnagar ◽  
Navin Rajesh

The manufacturing and storage of cefotaxime produces different impurities of various concentrations, which may influence the efficacy and safety of the drugs. Because no report of toxicity data is available on the impurities of cefotaxime, the present acute and genotoxicity studies were designed and conducted to provide the information for establishing the safety profile and qualification of the dimeric impurity. Histidine-requiring mutants of Salmonella typhimurium TA97a, TA98, TA100, TA102, and TA1535 strains, with or without metabolic activation (S-9), were used for point-mutation tests. Neither increase in numbers of revertants, indicative of mutagenic activity, nor inhibition of bacterial growth, indicative of cytotoxicity, was observed when the dimeric impurity of cefotaxime at concentrations of 0.62, 1.85, 5.56, 16.67, and 50 μg/plate was incorporated into plates containing S. typhimurium bacterial strains. Cultures of Chinese hamster ovary (CHO) cells at a cell density of 2 × 105 cells per culture were exposed to the dimeric impurity of cefotaxime at the concentration of 11.25, 22.5, and 45 mg per culture, with or without metabolic activation, and harvested at 18 h after exposure. No chromosomal aberrations in the cultured mammalian cells were recorded. Acute intramuscular administration of the dimeric impurity of cefotaxime in Sprague-Dawley rats did not result in any clinical signs and gross pathological changes up to 2000 mg/kg-body weight. The results of these studies indicated that the dimeric impurity of cefotaxime is nonmutagenic in Ames test, nonclastogenic in vitro, and acutely nontoxic in rats.


1991 ◽  
Vol 11 (6) ◽  
pp. 3125-3131
Author(s):  
B J Rollins ◽  
M E Sunday

The early growth response gene JE encodes a monocyte chemoattractant, MCP-1. The JE/MCP-1 protein attracts and stimulates human monocytes and induces monocyte-mediated inhibition of tumor cell growth in vitro. Expression of human or murine JE/MCP-1 in Chinese hamster ovary (CHO) cells completely suppressed their ability to form tumors in nude mice. Coinjection of JE/MCP-1-expressing cells with nonexpressing CHO cells or with HeLa cells also prevented tumor formation. Since JE/MCP-1 expression had no discernible effect on the tranformed phenotype of these cells in vitro, the suppressive effect depends on host animal factors. These factors are likely to be components of the inflammatory response, because JE/MCP-1-expressing cells elicited a predominantly monocytic infiltrate at the site of injection. Our results suggest that JE/MCP-1 protein may be useful in cancer therapy.


1988 ◽  
Vol 8 (8) ◽  
pp. 3476-3486 ◽  
Author(s):  
L Claesson-Welsh ◽  
A Eriksson ◽  
A Morén ◽  
L Severinsson ◽  
B Ek ◽  
...  

The structure of the human receptor for platelet-derived growth factor (PDGF) has been deduced through cDNA cloning. A 5.45-kilobase-pair cDNA clone predicts a 1,106-amino-acid polypeptide, including the cleavable signal sequence. The overall amino acid sequence similarity with the murine PDGF receptor is 85%. After transcription of the cDNA and translation in vitro, a PDGF receptor antiserum was used to immunoprecipitate a product of predicted size, which also could be phosphorylated in vitro. Stable introduction of the cDNA into Chinese hamster ovary (CHO) cells led to the expression of a 190-kilodalton component, which was immunoprecipitated by the PDGF receptor antiserum; this most probably represents the mature PDGF receptor. Binding assays with different 125I-labeled dimeric forms of PDGF A and B chains showed that the PDGF receptor expressed in CHO cells bound PDGF-BB and, to a lesser extent, PDGF-AB, but not PDGF-AA.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Noriko Yamano-Adachi ◽  
Rintaro Arishima ◽  
Sukwattananipaat Puriwat ◽  
Takeshi Omasa

Abstract Chinese hamster (Cricetulus griseus) ovary-derived Chinese hamster ovary (CHO) cells are the most commonly used mammalian hosts for the industrial production of recombinant therapeutics because of their ability to fold, assemble, and perform post-translational modifications, such as glycosylation, on proteins. They are also valuable for their ability to grow in serum-free suspension cultures. In this study, we established a cell line derived from lung tissue of Chinese hamsters, named Chinese hamster lung (CHL)-YN cells. The biosafety of CHL-YN cells was confirmed by in vitro sterility testing, mycoplasma detection, and reverse transcriptase assays. One of the key characteristics of CHL-YN cells was their doubling time of 8.1 h in chemically defined culture medium; thus, they proliferate much faster than conventional CHO cells and general mammalian cells. Transgenes could be introduced into CHL-YN cells with high efficiency. Finally, between 50% to > 100% of the amount of glycosylated immunoglobulin G (IgG)1 produced by CHO-K1 cells was produced by CHL-YN cells over a shorter period of time. In summary, fast-growing CHL-YN cells are a unique cell line for producing recombinant proteins.


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