Search results for "carcinogenicity"
showing 10 items of 11 documents
Detection of mammalian carcinogens with an immunological DNA synthesis-inhibition test.
1992
There is a close relationship between genotoxicity, mutagenicity and carcinogenicity. But the controversy of which short-term test system best recognizes human carcinogens is still going on. Currently, the Salmonella gene mutation assay ('Ames test') is the most widely used test for the screening of mutagens. However, many in vitro tests hold unsatisfactory validity data, presumably because of the inability of present short-term tests to detect non-genotoxic carcinogens, which are increasingly being brought into focus in the discussions of genesis of cancer. One principle often neglected in this context is the property of genotoxic agents to inhibit replicative DNA synthesis in (proliferati…
In vitro cytogenetic and genotoxic effects of curcumin on human peripheral blood lymphocytes
2012
International audience; Curcumin has shown a wide range of properties such as anti-inflammatory and anti-carcinogenic properties. Many of these effects, mainly the anti-carcinogenic effect, could be linked to its anti-oxidant effects. Nevertheless, some studies suggest that this natural compound possesses both pro- and anti-oxidative effects and that curcumin could be a genotoxic agent for some cell lines. We evaluated the genetic damage induced by curcumin to human lymphocytes exposed to increasing concentrations (0-50 μg/ml) of curcumin. Biomarkers such as chromosome aberrations (CAs) and sister chromatid exchange (SCE) were analyzed. In addition to the cytogenetic analysis, the effect of…
Carcinogenic aspect of xenobiotic molecules belonging to the peroxisome proliferator family.
1999
It is known that a short-term exposure of rat, mice or incubation of hepatic cells with fibrate molecules leads to increase in peroxisome number and cell hyperplasia. Further, long-term incubation of cells (at least a year) show transformed characteristics with foci and nodules. To explain the hepatocarcinogenic effect of peroxisome proliferators in rodents we studied the effect of peroxisome proliferators on rat liver oncogenes expression. Earlier, we reported an increase in liver and kidney mRNA level of c-myc and N-myc. Since several metabolic genes are activated by PPAR (peroxisome proliferators activated receptor) through a PPRE (peroxisome proliferator response element), we suggest th…
Classification or non-classification of substances with positive tumor findings in animal studies: Guidance by the German MAK commission
2019
One of the important tasks of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (known as the MAK Commission) is in the evaluation of a potential for carcinogenicity of hazardous substances at the workplace. Often, this evaluation is critically based on data on carcinogenic responses seen in animal studies and, if positive tumor responses have been observed, this will mostly lead to a classification of the substance under investigation into one of the classes for carcinogens. However, there are cases where it can be demonstrated with a very high degree of confidence that the tumor findings in the experimental animals are not relevant…
Problems Associated with the Use of Chemical Class Controls in Absence of Information on the Underlying Mechanism
1982
It is simply not possible to test all chemicals in adequately performed whole animal carcinogenicity tests. Short-term tests are, therefore, frequently used as a substitute. None of these short-term tests give results which correspond in all cases to the results obtained in whole animal carcinogenicity tests. Certain short-term tests have a notoriously poor predictibility for whole animal carcinogenicity for certain classes of chemicals. Therefore, if a chemical, whose carcinogenicity is unknown, is tested in a short-term test, frequently related compounds of known carcinogenicity are also tested simultaneously as chemical class controls.
Human Embryonic Stem Cell Derived Hepatocyte-Like Cells as a Tool for In Vitro Hazard Assessment of Chemical Carcinogenicity
2011
Hepatocyte-like cells derived from the differentiation of human embryonic stem cells (hES-Hep) have potential to provide a human relevant in vitro test system in which to evaluate the carcinogenic hazard of chemicals. In this study, we have investigated this potential using a panel of 15 chemicals classified as noncarcinogens, genotoxic carcinogens, and nongenotoxic carcinogens and measured whole-genome transcriptome responses with gene expression microarrays. We applied an ANOVA model that identified 592 genes highly discriminative for the panel of chemicals. Supervised classification with these genes achieved a cross-validation accuracy of > 95%. Moreover, the expression of the response g…
Tumor-initiating activity of the (+)-(S,S)- and (−)-(R,R)-enantiomers of trans-11,12-dihydroxy-11,12-dihydrodibenzo[a,l]pyrene in mouse skin
1999
Abstract A single administration of enantiomerically pure 11,12-dihydrodiols of dibenzo[ a,l ]pyrene (DB[ a,l ]P) on the back of NMRI mice and subsequent chronic treatment with 12- O -tetradecanoylphorbol 13-acetate (TPA) (initiation/promotion assay) revealed strikingly different carcinogenic activities of both enantiomers. Tumor-initiating activity of (−)-(11 R ,12 R )-DB[ a,l ]P-dihydrodiol, which is the metabolic precursor of the (−)- anti -(11 R ,12 S )-dihydrodiol (13 S ,14 R )-epoxide, was exceptionally higher than the corresponding effect of (+)-(11 S ,12 S )-DB[ a,l ]P-dihydrodiol, the metabolic precursor of (+)- syn -(11 S ,12 R )-dihydrodiol (13 S ,14 R )-epoxide. After topical ap…
Establishment and comparative characterization of novel squamous cell non-small cell lung cancer cell lines and their corresponding tumor tissue.
2010
Abstract Background Cell lines play an important role for studying tumor biology and novel therapeutic agents. Particularly in pulmonary squamous cell carcinoma (SCC) the availability of cell lines is limited and knowledge about their representativeness for corresponding tumor tissue is scanty. Materials and methods We established three novel SCC cell lines from fresh tumor tissue of 28 donors, including 8 SCC. Two cell lines were derived from different localizations of the same donor, i.e. primary tumor and lymph node metastasis. This represents a so far unique combination in lung cancer. The genotypes, gene expression profiles and mutational status of epidermal growth factor receptor ( EG…
Effect of some indole derivatives on xenobiotic metabolism and xenobiotic-induced toxicity in cultured rat liver slices.
1999
In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague-Dawley rats. While treatment of rat liver slices for 72 hours with 2-200 microM of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 microM 3,3'-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears…
Validation of the SOS/umu test using test results of 486 chemicals and comparison with the Ames test and carcinogenicity data
1996
The present study gives a comprehensive update of all umu genotoxicity assay results published so far. The available data of 486 chemicals investigated with the umu test are compared with the Ames test (274 compounds) as well as rodent carcinogenicity data (179 compounds). On the whole, there is good agreement between the umu test and the Ames test results, with a concordance of about 90%. The umu test was able to detect 86% of the Ames mutagens, while the Ames test (using at least 5 strains) detected 97% of the umu positive compounds. The elimination of TA102 from the set of Ames tester strains reduced the percentage of detectable umu genotoxins from 97 to 86%. The agreement between carcin…