nitrophenols and resorcinol

Accumulated evidence has shown that in vitro mammalian cell genotoxicity assays produce high frequencies of "misleading" positive results, i.e. predicted hazard is not confirmed in in vivo and/or carcinogenicity studies [1], raising the question of relevance to human risk assessment. A recent study of micronucleus (MN) induction [2] showed that commonly used p53-deficient rodent cell lines (CHL, CHO and V79) gave a higher frequency of "misleading" positive results with 9 non-DNA reactive, Ames-negative and in vivo negative chemicals [3] than human p53-competent cells (blood lymphocytes, TK6 and HepG2 cell lines). This raised the question of whether these differences were due to p53 status or species origin. This present study compared human versus mouse and p53-competent versus p53-mutated function. The same 9 chemicals were tested for induction of MN in mouse lymphoma L5178Y (mutated p53), human TK6 (functional p53) and WIL2-NS (TK6 related, with mutated p53) cells. Six chemicals provided clear positive increases in MN frequency in at least one cell type. L5178Y cells yielded clear positive responses with more chemicals than either TK6 or WIL2-NS, indicating origin rather than p53 functionality was most relevant. Apoptosis induction (measured via caspase-3/7) was also investigated with clear differences in the timing and extent of apoptosis induction between mouse and human cells noted. With curcumin in TK6 cells, induction of caspase-3/7 activity coincided with MN induction, whereas for L5178Y cells, MN induction occurred in the absence of increased caspase activity. By contrast, with MMS in TK6 cells, MN induction preceded increased caspase-3/7 activity. These data suggest that MN induction by "misleading positive" genotoxins in p53-competent human cell lines may result from apoptosis, whereas in p53-defective rodent cells such as L5178Y, MN induction may be independent of apoptosis.

Topics: Acrylates; Animals; Apoptosis; Cell Line; Cell Line, Tumor; Cell Survival; Chlorophenols; Curcumin; Cytochalasin B; DNA Damage; Dose-Response Relationship, Drug; Eugenol; Lymphocytes; Mice; Micronucleus Tests; Mutation; Nitrophenols; Organic Chemicals; ortho-Aminobenzoates; Phthalic Anhydrides; Propyl Gallate; Reproducibility of Results; Resorcinols; Tumor Suppressor Protein p53

A 4-chloro-3-nitrophenol (4C3NP)-mineralizing bacterium, Pseudomonas sp. JHN was isolated from a waste water sample collected from a chemically-contaminated area, India by an enrichment method. Pseudomonas sp. JHN utilized 4C3NP as a sole carbon and energy source and degraded it with the release of stoichiometric amounts of chloride and nitrite ions. Gas chromatography and gas chromatography-mass spectrometry detected 4-chlororesorcinol as a major metabolite of the 4C3NP degradation pathway. Inhibition studies using 2,2'-dipyridyl showed that 4-chlororesorcinol is a terminal aromatic compound in the degradation pathway of 4C3NP. The activity for 4C3NP-monooxygenase was detected in the crude extracts of the 4C3NP-induced JHN cells that confirmed the formation of 4-chlororesorcinol from 4C3NP. The capillary assay showed that Pseudomonas sp. JHN exhibited chemotaxis toward 4C3NP. The bioremediation capability of Pseudomonas sp. JHN was monitored to carry out the microcosm experiments using sterile and non-sterile soils spiked with 4C3NP. Strain JHN degraded 4C3NP in sterile and non-sterile soil with same degradation rates. This is the first report of (i) bacterial degradation and bioremediation of 4C3NP, (ii) formation of 4-chlororesorcinol in the degradation pathway of 4C3NP, (iii) bacterial chemotaxis toward 4C3NP.

Topics: Biodegradation, Environmental; Chromatography, High Pressure Liquid; Humans; India; Metabolic Networks and Pathways; Nitrophenols; Pseudomonas; Resorcinols; Soil Microbiology; Wastewater

The electrochemical oxidation of pesticide, o-nitrophenol (ONP) as one kind of pesticide that is potentially dangerous and biorefractory, was studied by galvanostatic electrolysis using boron-doped diamond (BDD) as anode. The influence of several operating parameters, such as applied current density, supporting electrolyte, and initial pH value, was investigated. The best degradation occurred in the presence of Na2SO4 (0.05 M) as conductive electrolyte. After 8h, nearly complete degradation of o-nitrophenol was achieved (92%) using BDD electrodes at pH 3 and at current density equals 60 mA cm(-2). The decay kinetics of o-nitrophenol follows a pseudo-first-order reaction. Aromatic intermediates such as catechol, resorcinol, 1,2,4-trihydroxybenzene, hydroquinone and benzoquinone and carboxylic acids such as maleic glycolic, malonic, glyoxilic and oxalic, have been identified and followed during the ONP treatment by chromatographic techniques. From these anodic oxidation by-products, a plausible reaction sequence for ONP mineralization on BDD anodes is proposed.

Topics: Benzoquinones; Boron; Carboxylic Acids; Catechols; Diamond; Electrodes; Electrolysis; Hydrogen-Ion Concentration; Hydroquinones; Kinetics; Models, Chemical; Nitrophenols; Oxygen; Pesticides; Resorcinols; Water Pollutants, Chemical; Water Purification

The predictions of mixture toxicity for chemicals are commonly based on two models: concentration addition (CA) and independent action (IA). Whether the CA and IA can predict mixture toxicity of phenolic compounds with similar and dissimilar action mechanisms was studied. The mixture toxicity was predicted on the basis of the concentration-response data of individual compounds. Test mixtures at different concentration ratios and concentration levels were designed using two methods. The results showed that the Weibull function fit well with the concentration-response data of all the components and their mixtures, with all relative coefficients (Rs) greater than 0.99 and root mean squared errors (RMSEs) less than 0.04. The predicted values from CA and IA models conformed to observed values of the mixtures. Therefore, it can be concluded that both CA and IA can predict reliable results for the mixture toxicity of the phenolic compounds with similar and dissimilar action mechanisms.

Topics: Benzyl Alcohols; Chlorophenols; Dose-Response Relationship, Drug; Drug Interactions; Environmental Pollutants; Hydroquinones; Nitrophenols; Phenols; Phloroglucinol; Resorcinols; Vibrio

Topics: Aldehydes; Benzaldehydes; Benzoates; Catechols; Chromatography; Cinnamates; Hippurates; Indoles; Mandelic Acids; Naphthalenes; Nitrophenols; Phenol; Phenols; Quinolines; Research; Resorcinols; Tryptamines