Microorganisms in the environment can often adapt to use xenobiotic chemicals as novel growth and energy substrates. Specialized enzyme systems and metabolic pathways for the degradation of man-made...Full Text Available
Numerous xenobiotics, including therapeutics agents, are substrates for bioactivation to electrophilic reactive intermediates that may covalently modify biomolecules. Selective estrogen receptor...Full Text Available
The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals,...Full Text Available
Carboxylesterases (CE) are ubiquitous enzymes that hydrolyze numerous ester-containing xenobiotics, including complex molecules, such as the anticancer drugs irinotecan (CPT-11) and capecitabine...Full Text Available
Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This...Full Text Available
BackgroundTransposons, i.e. transposable elements (TEs), are the major internal spontaneous mutation agents for the variability of eukaryotic genomes. To address the general issue...Full Text Available
The sensitivity of different renal regions to xenobiotics requires the development of a multiplex immunoassay for the simultaneous analysis of kidney biomarkers. Calbindin D28K is a distal tubule-specific...Full Text Available
Keap1 regulates Nrf2 activity in response to xenobiotic and oxidative stresses. Nrf2 is an essential regulator of cytoprotective genes. Keap1-null mice are lethal by weaning age due...Full Text Available
Free radical formation has been implicated in the toxicity of a wide range of xenobiotics. In recent years, particular interest has been paid to compounds which can undergo a one electron reduction...Full Text Available
The glutathione S-transferases (GSTs) are a family of isoenzymes involved in the detoxication of a variety of electrophilic xenobiotics. The present investigation demonstrates that GST activity and...Full Text Available
The use of municipal sewage sludge as a fertilizer in agriculture is a convenient method of disposal. However, sludge is often contaminated with toxic organic compounds such as dioxins, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs), with implications for soil fertility and quality of crops for human and animal consumption. These compounds can be assimilated by intact plants or in-vitro cell-Culture systems. The amount of uptake depends on the plant species and on the physico-chemical conditions that influence, for example, molecular configuration; uptake rates are higher with low-molecular-weight and polar compounds. The xenobiotic can be converted to polar conjugates and hydroxylated metabolites that may also be toxic. In some cases, large amounts of the compound and/or its metabolic products are incorporated into non-extractable residues. The bound residues, especially those associated with carbohydrate fractions of the cell wall, ...
The gastrointestinal (GI) tract is an important target organ for the toxicity of xenobiotics. The toxic effects of xenobiotics on this complex, heterogeneous structure have been difficult to model in vitro and have traditionally been assessed in vivo. The explant culture of GI tissue offers an alternative approach. Historically, the organotypic culture of the GI tract proved far more challenging than the culture of other tissues, and it was not until the late 1960s that Browning and Trier described the means by which intestinal tissues could be successfully cultured. This breakthrough provided a tool researchers could utilise, and adapt, to investigate topics such as the pathogenesis of inflammatory intestinal diseases, the effect of growth factors and cytokines on intestinal proliferation...
Hepatocyte nuclear factor (HNF) 4α is a key transcription factor regulating endo/xenobiotic-metabolizing enzymes and transporters. We investigated whether microRNAs are involved in the regulation...Full Text Available
The effects of eight chemicals on the inactivation rate of ultraviolet radiation on the colony building capabilities of two strains of Saccharomyces cervisae - a wild type strain and a mutant deficient in excision repair - were studied. The insecticide methoxychlor, the herbicide 2,4-dichlorophenoxyacetic acid, the fungicide pentachlorophenol and its metabolite tetrachlorohydroquinone, as well as the chemicals acrylonitrile and 2,3-dichloro-1-propene have no significant impact on the effects of UV radiation in Saccharomyces cerevisae. Depending on the concentration, trichloroethylene increases the sensitivity to UV radiation. The herbicide paraquat provides efficient protection against UV radiation at concentrations where a toxic effect cannot be observed even without UV. The results were rather similar for both strains. (orig.).
Abstract Lysis and extraction of cells are essential sample processing steps for investigations pertaining to metabolism of xenobiotics in cell culture studies. Of particular importance to these procedures are maintaining high lysis efficiency and analyte integrity as they influence the qualitative and quantitative distribution of drug and toxicant metabolites in the intra- and extracellular milieus. In this study we have compared the efficiency of different procedures viz. homogenization, sonication, bead beating, and molecular grinding resin treatment for disruption of HT-29 colon cells exposed to benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound and a suspected colon carcinogen. Also, we have evaluated the efficiency of various procedures for extracting BaP parent c...
Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-#kappa#B in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of the exposed mice, ...
The rate of hepatic cytochrome P450 Cypla1 and Cyp1a2 induction was investigated in C57BL male mice during induction with o-aminoazotoluene (OAT), benzo[a]pyrene (BP) and 1,4-dihydroxyanthraquinone (AQ). The Cypla1 mPNA level determined by quantitative RT-competitive PCR increased more than three orders of magnitude during induction with OAT and BP compared with untreated animals and remained unchanged during induction with AQ. The Cypla2 mRNA level was only 8.5, 18.7 and 1.9 times higher during induction with OAT, BP and AQ respectively than in untreated mice. At the same time 7-Ethoxyresorufin-O-deethylase (EROD) and 7-Methoxyresorufin-O-demethylase (MROD) activities of Cypla were also investigated in liver. The increase of Cypla1 mRNA level correlated with the increase of EROD activity. This suggests involvement of the transcriptional mechanism of the inducibility of this enzyme. In the case of Cypla2 there was insignificant increase of its mRNA level but high catalytic activity ...
The eastern oyster (Crassostrea virginica) developed neoplastic disorders when experimentally exposed both in the laboratory and field to chemically contaminated sediment from Black Rock Harbor (BRH), Bridgeport, Connecticut. Neoplasia was observed in oysters after 30 or 60 days of continuous exposure in a laboratory flow-through system to a 20 mg/L suspension of BRH sediment plus postexposure periods of 3, 30, or 60 days. Composite tumor incidence was 13.6% for both exposures. Tumor occurrence was highest in the renal excretory epithelium, followed in order by gill, gonad, gastrointestinal, heart, and embryonic neural tissue. Regression of experimental neoplasia was not observed when the stimulus was discontinued. In field experiments, gill neoplasms developed in oysters, deployed in cages for 30 days at BRH and 36 days at a BRH dredge material disposal area in Central Long Island Sound, and kidney and gastrointestinal neoplasms developed in caged oysters deployed 40 days in Quincy ...