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Genotoxicity occurring at the target organs of carcinogenesis is important for understanding the mechanisms of chemical carcinogenicity and also for setting of threshold estimation. In vivo gene mutations have been evaluated by transgenic animal models in which any organ can be targeted; however, the methodologies that have been applied to assess chromosomal aberrations including micronucleus induction, are organ restricted, (often to bone marrow hematopoietic cells, as a common example). For food and food-related chemicals, the digestive tract is the important target organ as it is the organ of first contact. In the present study, we used 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 1,2-dimethylhydrazine (DMH) as model chemicals of carcinogens primarily targeting the colon. We evaluated the applicability of colon cells and hepatocytes, together with bone marrow cells, in the micronucleus assay. Both model chemicals induced micronuclei in the colon, which is the target organ of these carcinogens, after short- and long-term treatment(s). The results demonstrate the target specificity of micronucleus induction and the assay using organs other than bone marrow will play an important role in understanding the mechanism of carcinogenicity and predicting new carcinogenic agents.
This article was published in the following journal.
Name: Regulatory toxicology and pharmacology : RTP
Methylation is one of the important post translational modifications of biological systems. At the metabolite level, the methylation process is expected to convert bioactive compounds such as amino ac...
The present study was aimed to investigate the effect of 2-amino-4-(1-piperidine) pyridine on migration and invasion of colon cancer cells. Treatment of colon cancer cells with 2-amino-4-(1-piperidine...
The Tradescantia micronucleus assay has been used since 50 years for the detection of genotoxins (including carcinogens) in the environment. A large database concerning the effects of individual chem...
The classical in vitro genotoxicity test battery is known to be sensitive for indicating genotoxicity. However, a high rate of "misleading" positives was reported when three assays were combined as re...
Positron emission tomography (PET) imaging with F-labeled α-methyl-substituted amino acids exerts significant influence on differential diagnosis of malignant tumors and tumor-like lesions. Exclusive...
The proposed study will assess the combined effect of perampanel and ketamine on the anti-depressant response in individuals with treatment resistant depression. The purpose of this study ...
Adjuvant N-methyl-D-aspartic acid (NMDA)-enhancing agents, such as GlyT-1 inhibitors and NMDA-glycine site agonists have been demonstrated to be beneficial for chronic schizophrenia patien...
This extended access study will assess the long-term safety and tolerability of bardoxolone methyl in qualified patients with chronic kidney disease (CKD) who previously participated in on...
This trial screens patients with colon or rectal cancer that has spread to other places in the body or cannot be removed by surgery for genetic mutations for recommendation to a molecularl...
The good clinical practice guidelines for the surveillance of workers after occupational exposure to lung carcinogens were approved by the Haute Autorité de la Santé (French National Aut...
Any of three isomeric compounds (ortho-, meta-, and para-) containing a benzene ring with a methyl and amino group attached to it. They are suspected CARCINOGENS.
The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.
Induction and quantitative measurement of chromosomal damage leading to the formation of micronuclei (MICRONUCLEI, CHROMOSOME-DEFECTIVE) in cells which have been exposed to genotoxic agents or IONIZING RADIATION.
The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.
3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2- hydroxyethyl)-4-methylthiazolium chloride.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...