Toxicology Research - Forensic Toxicology, Carcinogenicity, Assays

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Lack of constitutive and inducible ethoxyresorufin-O-deethylase activity in the liver of suckermouth armored catfish (Hypostomus affinis and Hypostomus auroguttatus, Loricariidae).

Parente TE, De-Oliveira AC, Beghini DG, Chapeaurouge DA, Perales J, Paumgartten FJ

Laboratory of Environmental Toxicology, Department of Biological Sciences, National School of Public Health, Av Brasil 4036 (EXCAM), Rio de Janeiro, RJ 21040-361, Brazil.

We investigated the presence and inducibility of CYP1A in suckermouth catfish (Hypostomus affinis and Hypostomus auroguttatus, Loricariidae), tilapia (Oreochromis niloticus, Cichlidae) and mice (Mus musculus, Muridae). Alkoxyresorufin-O-dealkylases (EROD, MROD, PROD and BROD) were detected and proved to be inducible (beta-naphthoflavone, BNF or dimethylbenz[a]anthracene, DMBA, 50 mg/kg bw ip) in liver microsomes from tilapia and mice. In loricariids, alkoxyresorufin-O-dealkylases were either undetectable (MROD/EROD) or very low (PROD/BROD), and so they remained after treatment with BNF or DMBA. Ethoxycoumarin-O-deethylase (ECOD) was recorded in all species and proved not to be inducible by BNF or DMBA. In loricariids and tilapia, ECOD was not depressed by a concentration of alpha-naphthoflavone (CYP1A-inhibitor) that markedly depressed EROD in tilapia. A CYP1A-like protein was detected by a monoclonal antibody in rats, mice and tilapia, but not in loricariids. A polyclonal antibody, however, detected a CYP1A-like protein in liver microsomes of loricariids. Suckermouth catfish, rats, mice and tilapia express a protein reactive with a polyclonal antibody against trout CYP3A. Loricariids and tilapia exhibited marked genotoxic responses (enhanced incidence of micronucleated erythrocytes) following treatment DMBA (50 mg/kg bw ip), a promutagen activated by CYP1A/1B. Therefore, although not exhibiting EROD, a CYP1A-mediated activity, loricariids converted DMBA into its genotoxic metabolites. Our findings suggest that the CYP1A-like protein of locariid catfish recognizes DMBA, but not ethoxyresorufin, as a substrate.

Published 22 June 2009 in Comp Biochem Physiol C Toxicol Pharmacol.
Full-text of this article is available online (may require subscription).


Articles on Toxicology published 22 June 2009:

Real-time in vivo imaging of mercury uptake in Caenorhabditis elegans through the foodchain.   Toxicology, 261(3): 136-42.

Mercury is a strong poison that poses significant and immediate hazards to human health. Due to its bioaccumulative properties, even small amounts of the metal are usually very poisonous or lethal when absorbed over long periods of time. Even though the possible dangers of mercury interactions with proteins are well understood, little is known about its uptake and dynamics within an organism. In particular, the concentration and distribution of the metal within a cell or a tissue are only ... [Abstract] [Full-text]

Role of Paris PM(2.5) components in the pro-inflammatory response induced in airway epithelial cells.   Toxicology, 261(3): 126-35.

Particulate matter (PM) is suspected to play a role in environmentally-induced pathologies. Due to its complex composition, the contribution of each PM components to PM-induced biological effects remains unclear. Four samples of Paris PM(2.5) having different polyaromatic hydrocarbons and metals contents were compared with each other and with their respective aqueous and organic extracts used alone or in combination. The four PM(2.5) samples similarly induced granulocyte macrophage-colony ... [Abstract] [Full-text]

Anti-thyroid hormone activity of bisphenol A, tetrabromobisphenol A and tetrachlorobisphenol A in an improved reporter gene assay.   Toxicol In Vitro.

Previously, we transiently transfected Gal4-fused thyroid hormone receptor (TR) expressing vector and the Gal4 response reporter structure pUAS-tk-luc into HepG2 cell, developed a TR beta-1 mediated reporter gene assay to screen for compounds that acted on the TR signaling pathway. In this study, we improved the test efficiency by changing the transfected cell line into CV-1 cell. Triiodothyronine (T3) and thyroxine (T4) induced higher luciferase expression, with the median effective ... [Abstract] [Full-text]

Synthesis, structure characterization, and enzyme screening of clenbuterol glucuronides.   Eur J Pharm Sci, 37(5): 581-7.

Two clenbuterol O-glucuronide diastereomers were synthesized by the Koenigs-Knorr reaction. Structures and glucuronidation sites of the glucuronides were characterized by tandem mass spectrometry and nuclear magnetic resonance spectroscopy. The two diastereomers were used as standard compounds in studies of stereoselective glucuronidation of clenbuterol with liver microsomes from different species and with 15 human recombinant UDP-glucuronosyltransferases. In this study, chemical and enzymatic ... [Abstract] [Full-text]

The Aryl-hydrocarbon receptor does not require the p23 co-chaperone for ligand binding and target gene expression in vivo.   Toxicol Lett, 189(1): 57-62.

The Aryl-hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates most of the toxic affects of 2,3,7,8-tetrachlorodibenzo-(p)-dioxin (TCDD) and other xenobiotic compounds. The AHR cytoplasmic complex consists of two molecules of HSP90 and at least one molecule of Hepatitis B Virus-X associated protein 2 and the co-chaperone p23. With the use of in vitro model systems, p23 has been shown previously to be important to maintaining the efficient ligand binding and ... [Abstract] [Full-text]

Enantiomer-specific, bifenthrin-induced apoptosis mediated by MAPK signalling pathway in Hep G2 Cells.   Toxicology, 261(3): 119-25.

Enantioselectivity in toxicology, and health risk of chiral xenobiotics have become important topics at the forefront of chemistry and toxicology research. Our previous results showed that cis-bifenthrin (cis-BF) induced cytotoxicity and genotoxicity in human amnion epithelial (FL) cells, in an enantioselective manner. However, the exact molecular mechanisms of synthetic pyrethroid-induced, enantioselective apoptosis and cytotoxicity remain unclear. In this study, enantiomers of the synthetic ... [Abstract] [Full-text]

Gambogic acid induces G0/G1 arrest and apoptosis involving inhibition of SRC-3 and inactivation of Akt pathway in K562 leukemia cells.   Toxicology.

Gambogic acid (GA), a major active component of gamboge, exhibits potent anticancer activity in many kinds of cancer cells. However, the anticancer mechanism of GA is not clearly understood. Here we showed that GA could cause growth inhibition, induce the G0/G1 phase cell cycle arrest and apoptosis in human chronic myelogenous leukemia cell line K562 cells. Since steroid receptor coactivator-3 (SRC-3), overexpressed in many human malignancies including leukemia, is a central target for cancer ... [Abstract] [Full-text]

3,3'-Diindolylmethane induces a G(1) arrest in human prostate cancer cells irrespective of androgen receptor and p53 status.   Biochem Pharmacol.

3,3'-Diindolylmethane (DIM) is a potential chemopreventive phytochemical derived from Brassica vegetables. In this study we characterized the effect of DIM on cell cycle regulation in both androgen-dependent LNCaP and androgen receptor negative p53 mutant DU145 human prostate cancer cells. DIM had an anti-proliferative effect on both LNCaP and DU145 cells, as it significantly inhibited [(3)H]-thymidine incorporation. FACS analysis revealed a DIM-mediated G(1) cell cycle arrest. DIM strongly ... [Abstract] [Full-text]


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