Kegg Pathway: 1,4-Dichlorobenzene degradation

Environ Sci Technol. 2009 Jul 1; 43(13): 4843-50
Barber LB, Keefe SH, Leblanc DR, Bradley PM, Chapelle FH, Meyer MT, Loftin KA, Kolpin DW, Rubio F

Organic wastewater contaminants (OWCs) were measured in samples collected from monitoring wells located along a 4.5-km transect of a plume of groundwater contaminated by 60 years of continuous rapid infiltration disposal of wastewater treatment plant effluent. Fifteen percent of the 212 OWCs analyzed were detected, including the antibiotic sulfamethoxazole (SX), the nonionic surfactant degradation product 4-nonylphenol (NP), the solvent tetrachloroethene (PCE), and the disinfectant 1,4-Dichlorobenzene (DCB). Comparison of the 2005 sampling results to data collected from the same wells in 1985 indicates that PCE and DCB are transported more rapidly in the aquiferthan NP, consistent with predictions based on compound hydrophobicity. Natural gradient in situ tracer experiments were conducted to evaluate the subsurface behavior of SX, NP, and the female sex hormone 17beta-estradiol (E2) in two oxic zones in the aquifer: (1) a downgradient transition zone at the interface between the contamination plume and the overlying uncontaminated groundwater and (2) a contaminated zone located beneath the infiltration beds, which have not been loaded for 10 years. In both zones, breakthrough curves for the conservative tracer bromide (Br-) and SX were nearly coincident, whereas NP and E2 were retarded relative to Br- and showed mass loss. Retardation was greater in the contaminated zone than in the transition zone. Attenuation of NP and E2 in the aquifer was attributed to biotransformation, and oxic laboratory microcosm experiments using sediments from the transition and contaminated zones show that uniform-ring-labeled 14C 4-normal-NP was biodegraded more rapidly 130-60% recovered as 14CO2 in 13 days) than 4-14C E2 (20-90% recovered as 14CO2 in 54 days). There was little difference in mineralization potential between sites.

Mutat Res. 2009 Sep-Dec; 682(2-3): 94-109
Hernández LG, van Steeg H, Luijten M, van Benthem J

It is well established that cancer is a multi-step process which involves initiation, promotion and progression. Chemical carcinogens can alter any of these processes to induce their carcinogenic effects. The presence of multiple mutations in critical genes is a distinctive feature of cancer cells and supports the contention that cancer arises through the accumulation of irreversible DNA damage. In the majority of instances, chemical carcinogens, directly or after xenobiotic metabolism, induce DNA damage and act in a 'genotoxic' manner. There is, however, a group of carcinogens that induce cancer via non-genotoxic mechanisms. Non-genotoxic carcinogens have been shown to act as tumor promoters (1,4-Dichlorobenzene), endocrine-modifiers (17beta-estradiol), receptor-mediators (2,3,7,8-tetrachlorodibenzo-p-dioxin), immunosuppressants (cyclosporine) or inducers of tissue-specific toxicity and inflammatory responses (metals such as arsenic and beryllium). The diversity of modes of action of non-genotoxic carcinogens, the tissue and species specificity, and the absence of genotoxicity makes predicting their carcinogenic potential extremely challenging. In order to better understand the mechanisms of known human non-genotoxic carcinogens and to illustrate the importance of a weight of evidence approach when evaluating their carcinogenic potential, we will (1) evaluate the proportion of non-genotoxic carcinogens among known, probable and possible human carcinogens classified by the International Agency for Research on Cancer (IARC), (2) estimate the risk of exposure of human non-genotoxic carcinogens through margin of exposure (MOE) evaluation, and (3) discuss potential alternative methods for their detection. Our analysis demonstrated that human non-genotoxic carcinogens were present in 12% (45/371) of IARC's Groups 1, 2A and 2B carcinogens and that a potential hazard was associated with 27% (12/45) of them. Consequently, it is suggested that for all genotoxic chemicals, the mode of action is investigated for hazard and risk evaluation. Further, if negative genotoxic compounds have putative non-genotoxic modes of action, appropriate risk measures should be implemented.

BMC Genomics. 2009; 10: 272
Chou JW, Bushel PR

BACKGROUND: Hepatotoxicity is a form of liver injury caused by exposure to stressors. Genomic-based approaches have been used to detect changes in transcription in response to hepatotoxicants. However, there are no straightforward ways of using co-expressed genes anchored to a phenotype or constrained by the experimental design for discerning mechanisms of a biological response. RESULTS: Through the analysis of a gene expression dataset containing 318 liver samples from rats exposed to hepatotoxicants and leveraging alanine aminotransferase (ALT), a serum enzyme indicative of liver injury as the phenotypic marker, we identified biological processes and molecular pathways that may be associated with mechanisms of hepatotoxicity. Our analysis used an approach called Coherent Co-expression Biclustering (cc-Biclustering) for clustering a subset of genes through a coherent (consistency) measure within each group of samples representing a subset of experimental conditions. Supervised biclustering identified 87 genes co-expressed and correlated with ALT in all the samples exposed to the chemicals. None of the over-represented pathways related to liver injury. However, biclusters with subsets of samples exposed to one of the 7 hepatotoxicants, but not to a non-toxic isomer, contained co-expressed genes that represented pathways related to a stress response. Unsupervised biclustering of the data resulted in 1) four to five times more genes within the bicluster containing all the samples exposed to the chemicals, 2) biclusters with co-expression of genes that discerned 1,4 dichlorobenzene (a non-toxic isomer at low and mid doses) from the other chemicals, pathways and biological processes that underlie liver injury and 3) a bicluster with genes up-regulated in an early response to toxic exposure. CONCLUSION: We obtained clusters of co-expressed genes that over-represented biological processes and molecular pathways related to hepatotoxicity in the rat. The mechanisms involved in the response of the liver to the exposure to 1,4-Dichlorobenzene suggest non-genotoxicity whereas the exposure to the hepatotoxicants could be DNA damaging leading to overall genomic instability and activation of cell cycle check point signaling. In addition, key pathways and biological processes representative of an inflammatory response, energy production and apoptosis were impacted by the hepatotoxicant exposures that manifested liver injury in the rat.

Environ Res. 2009 Feb; 109(2): 193-9
Liu J, Drane W, Liu X, Wu T

This study was to explore the relationships between personal exposure to 10 volatile organic compounds (VOCs) and biochemical liver tests with the application of canonical correlation analysis. Data from a subsample of the 1999-2000 National Health and Nutrition Examination Survey were used. Serum albumin, total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) served as the outcome variables. Personal exposures to benzene, chloroform, ethylbenzene, tetrachloroethene, toluene, trichloroethene, o-xylene, m-,p-xylene, 1,4-Dichlorobenzene, and methyl tert-butyl ether (MTBE) were assessed through the use of passive exposure monitors worn by study participants. The first two canonical correlations were 0.3218 and 0.2575, suggesting a positive correlation mainly between the six VOCs (benzene, ethylbenzene, toluene, o-xylene, m-,p-xylene, and MTBE) and the three biochemical liver tests (albumin, ALP, and GGT) and a positive correlation mainly between the two VOCs (1,4-Dichlorobenzene and tetrachloroethene) and the two biochemical liver tests (LDH and TB). Subsequent multiple linear regressions show that exposure to benzene, toluene, or MTBE was associated with serum albumin, while exposure to tetrachloroethene was associated with LDH and total bilirubin. In conclusion, exposure to certain VOCs as a group or individually may influence certain biochemical liver test results in the general population.

Toxicology. 2008 Nov 20; 253(1-3): 28-35
Yan RM, Chiung YM, Pan CY, Liu JH, Liu PS

para-Dichlorobenzene (DCB), a deodorant and an industrial chemical, is a highly volatile compound and is known to be an indoor air contaminant. Because of its widespread use and volatility, the toxicity of DCB presents a concern to industrial workers and public. Some toxic aspects of DCB have already been focused but its effects on neuronal signal transduction have been hitherto unknown. The effects of DCB on the cytosolic calcium homeostasis are investigated in human neuroblastoma SH-SY5Y cells in this study. DCB, above 200 microM, was found to induce a rise in cytosolic calcium concentration that could not be counteracted by nicotinic acetylcholine receptor (nAChR) and muscarinic acetylcholine receptor (mAChR) antagonists but was partially inhibited by thapsigargin. To understand the actions of DCB on the acetylcholine receptors, we investigated its effects on the changes of cytosolic calcium concentration following nicotinic AChR stimulation with epibatidine and muscarinic AChR stimulation with methacholine in human neuroblastoma SH-SY5Y cells. DCB inhibited the cytosolic calcium concentration rise induced by epibatidine and methacholine with respective IC(50)s of 34 and 294 microM. The inhibitions of DCB were not the same as thapsigargin's inhibition. In the electrophysiological observations, DCB blocked the influx currents induced by epibatidine. Our findings suggest that DCB interferes with the functional activities of AChR, including its coupling influx currents and cytosolic calcium elevations.

J Hazard Mater. 2009 Mar 15; 162(2-3): 899-905
Gomathi Devi L, Krishnamurthy G

Gas chromatograph-mass spectroscopic identification of intermediate products in the degradation of diclofop-methyl and the kinetics of the reaction has been investigated. Formation of 4-[(2,4-dichlorophenoxy) phenoxy] ethane and (2,4-dichlorophenoxy) phenol was investigated. The other intermediate products are 2,4-dichlorophenol, 2,4-dichlorobenzene, phenol and acetic acid have been ascertained. The decrease in the concentration of the parent/intermediate compounds is followed by UV-vis spectral study and the supportive information on the functional groups in the intermediates has been obtained from IR-spectroscopy. degradation process proceeds with oxidation-reduction reaction by the attack of OH*, H*, O(2)*(-) free radicals, which are photogenerated on the UV-light illuminated TiO(2)/BaTiO(3) photocatalysts particles in aqueous medium. In this presentation another wide band gap semiconductor BaTiO(3) is shown to have comparable photocatalytic efficiency. The oxidizing agents are added to accelerate the rate of the reaction by enhancing the formation of free radicals. Based on the intermediates formed in the process of degradation, a suitable mechanism has been proposed.

Environ Toxicol. 2009 Feb; 24(1): 43-8
Ma X, Havelka MM

Healthy growth of plants is a prerequisite for successful application of phytoremediation technologies. Typha angustifolia and Phragmites communis are common wetland plants and have shown potential for phytoremediation of hexachlorobenzene (HCB). However, the lack of phytotoxicity data impedes their application in field sites. This study investigated the phytotoxicity of HCB, and its two metabolites: 1,3,5-trichlorobenzene (1,3,5-TCB) and 1,4-Dichlorobenzene (1,4-DCB) to Typha and the phytotoxicity of 1,3,5-TCB to Phragmites. The phytotoxicity of 1,3,5-TCB is species-dependent, with Typha demonstrating significantly higher tolerance than Phragmites. The concentration of 1,3,5-TCB causing zero growth of Phragmites was determined to be 1575 mg TCB/kg dry sediment. The concentration has to be doubled to completely inhibit the growth of Typha. Adverse effects of chlorinated benzenes in sediments on Typha increased with decreasing chlorine atoms. The concentrations causing zero growth of Typha are 5765 mg HCB/kg dry soil, 3157 mg 1,3,5-TCB/kg dry soil, and 1325 mg 1,4-DCB/kg dry soil. The higher toxicity of 1,4-DCB than 1,3,5-TCB and HCB in sediment was ascribed to its higher availability and easiness to be taken up by plants. The conclusion was supported by both growth rate calculations and plant height measurements. (c) 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.

Environ Toxicol. 2008 Apr; 23(2): 184-92
Monferran MV, Pesce SF, Cazenave J, Wunderlin DA

We report changes in activities of detoxification and antioxidant enzymes as well as lipid peroxidation levels in liver, gills, and brain of Jenynsia multidentata exposed to 1,2- and 1,4-Dichlorobenzene (DCB). Fish were captured at an unpolluted area, transported to the laboratory, and acclimated previous to experiments. Exposures were carried out using 1,2-DCB at 0.5, 1, 5, and 10 mg L(-1) and 1,4-DCB at 0.05, 0.1, 1, and 5 mg L(-1). After 24-h exposure, fish were sacrificed and dissected separating liver, gills, and brain of each fish. Organs were used for enzyme extractions, evaluating antioxidant system through the assay of glutathione reductase, guaiacol peroxidase, glutathione peroxidase, catalase as well as detoxification system by measuring glutathione-S-transferase (GST) activity. Additionally, thiobarbituric acid reactive substances (TBARS) method was used to evaluate the peroxidation of lipids. No changes in GST activity were found in liver of fish exposed to DCBs but in gills and brain of exposed fish. The detoxification system was activated at lower concentrations of 1,2-DCB than 1,4-DCB. Antioxidant response is activated in liver at low DCB concentrations, followed by a drop at highest levels. We also found activation of the antioxidant system in gills and brain of exposed fish. On the other hand, we did not observe changes in TBARS concentrations in liver or gills of exposed fish with respect to controls, but in brain of fish exposed to 1,2-DCB (> or =0.5 mg L(-1)) and 1,4-DCB (5 mg L(-1)). Responses of both detoxification and antioxidant systems of J. multidentata suggest that 1,2-DCB is more toxic than 1,4-DCB to this specie. To the extent of our knowledge, this is the first report of oxidative stress induced by DCBs in fish. Our results evidence that the brain is the organ most severely affected by the oxidative stress caused by DCBs.

Chemosphere. 2008 Mar; 71(4): 711-6
De Coensel N, Desmet K, Sandra P, Górecki T

Moth repellent agents are considered major contributors to indoor air pollution. In this study, the chemical contamination of clothes due to their direct or indirect exposure to moth repellent agents such as p-dichlorobenzene, naphthalene and camphor were investigated. Cotton cloths were used as clothing simulant. They were analyzed using ultrasonic extraction followed by GC-MS analysis. Extrapolated results indicate that a regular cotton shirt indirectly exposed to these chemicals in a storage cabinet can contain up to 7, 3 and 7.5mg of p-dichlorobenzene, naphthalene and camphor, respectively, even after one-hour of airing. Passive sorptive sampling using polydimethylsiloxane-coated stir-bars and ultrasonic extraction followed by GC-MS analysis was used to monitor the concentration distribution in a wardrobe.

J Expo Sci Environ Epidemiol. 2008 Jul; 18(4): 421-9
Lin YS, Egeghy PP, Rappaport SM

The relationships between levels of volatile organic compounds (VOCs) in blood and air have not been well characterized in the general population where exposure concentrations are generally at parts per billion levels. This study investigates relationships between the levels of nine VOCs, namely, benzene, chloroform, 1,4-Dichlorobenzene, ethylbenzene, methyl tert-butyl ether (MTBE), tetrachloroethene, toluene, and m-/p- and o-xylene, in blood and air from a stratified random sample of the general US population. We used data collected from 354 participants, including 89 smokers and 265 nonsmokers, aged 20-59 years, who provided samples of blood and air in the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Demographic and physiological characteristics were obtained from self-reported information; smoking status was determined from levels of serum cotinine. Multiple linear regression models were used to investigate the relationships between VOC levels in air and blood, while adjusting for effects of smoking and demographic factors. Although levels of VOCs in blood were positively correlated with the corresponding air levels, the strength of association (R(2)) varied from 0.02 (ethylbenzene) to 0.68 (1,4-DCB). Also the blood-air relationships of benzene, toluene, ethylbenzene, and the xylenes (BTEX) were influenced by smoking, exposure-smoking interactions, and by gender, age, and BMI, whereas those of the other VOCs were not. Interestingly, the particular exposure-smoking interaction for benzene was different from those for toluene, ethylbenzene, and the xylenes. Whereas smokers retained more benzene in their blood at increasing exposure levels, they retained less toluene, ethylbenzene, and xylenes at increasing exposure levels. Investigators should consider interaction effects of exposure levels and smoking when exploring the blood-air relationships of the BTEX compounds in the general population.

Environ Sci Technol. 2007 Nov 1; 41(21): 7523-9
Zhu BW, Lim TT

Monochlorobenzene (MCB), dichlorobenzenes (DCBs), and 1,2,4-trichlorobenzene (124TCB) dechlorination experiments in water were carried out with freshly synthesized Pd/Fe particles. The pre- and postreacted Pd/Fe samples were characterized by applying various analytical techniques (XRD, SEM, TEM, and XPS). Chlorinated benzenes could be completely reduced by the Pd/Fe to benzene and the reaction followed the pseudo-first-order kinetics. The reaction rates followed the order TCB < DCBs < MCB, while among the DCBs the order was 1,4-Dichlorobenzene >1,3-dichlorobenzene > or = 1,2-dichlorobenzene. Insignificant reactions were observed with the unpalladized iron, suggesting that Pd was the only reactive site in the Pd/Fe particles. The aged Pd/Fe particles exhibited significant decrease in its dechlorination reactivity. The loss of Pd/Fe reactivity could be due to Pd dislodgment from the aged Pd/Fe particles and Pd islets encapsulation by the iron oxides film developed over aging period. Reactivity of the aged Pd/Fe could be only partially restored after HCI treatment, while regeneration with the NaBH4 reduction method could not restore its activity, although zerovalent state of the iron was reinstated.

J Hazard Mater. 2008 May 30; 153(3): 1136-41
Selli E, Bianchi CL, Pirola C, Cappelletti G, Ragaini V

The rate of 1,4-Dichlorobenzene (1,4-DCB) degradation and mineralization in the aqueous phase was investigated either under direct photolysis or photocatalysis in the presence of commercial or sol-gel synthesized TiO2, or under sonolysis at 20 kHz with different power inputs. Two lamps, both emitting in the 340-400 nm wavelength range with different energy, were employed as irradiation sources. Photocatalysis ensured faster removal of 1,4-DCB with respect to sonolysis and direct photolysis. The highest degradation and mineralization rate was attained with the combined use of photocatalysis and sonolysis, i.e. under sonophotocatalytic conditions. The efficiency of the employed advanced oxidation techniques in 1,4-DCB degradation is discussed also in relation to their energy consumption, which might be decisive for their practical application.

J Toxicol Environ Health B Crit Rev. 2007 Oct; 10(7): 467-526
Aronson DB, Bosch S, Gray DA, Howard PH, Guiney PD

A comparison of the human health risk to consumers using one of two types of toilet rimblock products, either a p-dichlorobenzene-based rimblock or two newer fragrance/surfactant-based alternatives, was conducted. Rimblock products are designed for global use by consumers worldwide and function by releasing volatile compounds into indoor air with subsequent exposure presumed to be mainly by inhalation of indoor air. Using the THERdbASE exposure model and experimentally determined emission data, indoor air concentrations and daily intake values were determined for both types of rimblock products. Modeled exposure concentrations from a representative p-dichlorobenzene rimblock product are an order of magnitude higher than those from the alternative rimblock products due to its nearly pure composition and high sublimation rate. Lifetime exposure to p-dichlorobenzene or the subset of fragrance components with available RfD values is not expected to lead to non-cancer-based adverse health effects based on the exposure concentrations estimated using the THERdbASE model. A similar comparison of cancer-based effects was not possible as insufficient data were available for the fragrance components.

Arch Toxicol. 2007 Jul; 81(7): 505-17
Takahashi O, Oishi S, Yoneyama M, Ogata A, Kamimura H

A significant increase/decrease in uterine and ovarian weights was occasionally seen in immature mice and rats subcutaneously administered paradichlorobenzene (PDCB) at doses of 22-67 mg/kg/day, but the results were not necessarily reproducible. PDCB at a dose of 800 mg/kg/day always reduced uterine and ovarian weights. Intraperitoneal PDCB at doses more than 400 mg/kg/day significantly inhibited the uterotrophic effect of beta-estradiol (E2) in CD-1 (ICR) mice. E2-induced uterotrophy was dose-dependently prevented by 204-400 mg PDCB/kg/day in C57BL/6N (Ah responsive) mice but not DBA/2N (Ah non-responsive) mice. While PDCB did not bind to estrogen receptor (ER(alpha)) up to 10(-3) M. Hepatic ethoxyresorufin-O-deethylase in adult female C57BL/6N mice was induced by i.p. administration of PDCB. Induction activity of PDCB may be 10(5)-10(6) times lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. These results suggest that PDCB is a weak antiestrogenic/antiuterotrophic compound possibly due to ER modulation through arylhydrocarbon receptor.

Arch Environ Occup Health. 2006 Jan-Feb; 61(1): 17-25
Wu T, Bhanegaonkar AJ, Flowers JW

The authors analyzed data from a national sample to examine the relationships between blood concentrations of selected volatile organic compounds (VOCs) and the assessment scores of neurobehavioral evaluation tests. They calculated summary statistics to describe blood concentrations of 30 VOCs. For instance, the 95th percentiles were as follows: 1,1,1-trichloroethane, 0.799 microg/l; 1,4-Dichlorobenzene, 11.081 microg/l; benzene, 0.476 microg/l; and toluene, 0.281 microg/l. For 1,4-Dichlorobenzene, benzene, dibromochloromethane, and trichloroethene, a blood level higher than the 95th percentile was associated with a poorer neurobehavioral assessment score than was a blood level up to the 95th percentile. The authors found a linear relationship between blood toluene concentration and the Serial Digit Learning Test score. The findings suggest that exposure to certain VOCs may result in poor neurobehavioral performance. The study was exploratory and precludes a conclusive statement, so further investigation is warranted.

Chemosphere. 2007 Aug; 68(11): 2073-9
Monferran MV, Wunderlin DA, Nimptsch J, Pflugmacher S

We report the effects of 1,2- and 1,4-Dichlorobenzene (1,2-DCB and 1,4-DCB) on the aquatic macrophyte Ceratophyllum demersum. We evaluated the response of the antioxidant system through the assay of glutathione reductase (GR), guaiacol peroxidase (POD) and glutathione peroxidase (GPx). Additionally, the effect of DCBs on the detoxication system by measuring the activity of glutathione-S-transferase (GST) was evaluated. C. demersum showed elevated GST activities when exposed to 10 and 20 mg l(-1) 1,2-DCB, and at 10 mg l(-1) for 1,4-DCB. These results show that glutathione conjugation take place at relatively high concentrations of both isomers. Significantly increased activities of POD were also detected in C. demersum exposed to concentrations above 5 mg l(-1) of the corresponding isomer. The GR activity was enhanced in plants exposed to 1,2-DCB (5 mg l(-1)) and 1,4-DCB (10 mg l(-1)). GPx was also significantly increased in exposures to the corresponding isomer, each at a concentration of 10 mg l(-1). However, plants exposed to low doses of 1,4-DCB (1 mg l(-1)) showed significantly decreased activities of both enzymes GR and GPx. Consequently, it is clear that the exposure of the aquatic macrophyte C. demersum to DCBs is able to cause an activation of the antioxidant system, showing an isomer specific pattern, which suggests that the defence system of this plant is playing an important role in scavenging ROS, helping to protect the organism against adverse oxidative effects generated by the prooxidant action of the tested xenobiotics. Furthermore, increased GST activities give indirect evidence on the conjugation of either DCBs or the corresponding metabolites during phase II of detoxication, which supports the elimination process of toxic metabolites from cells of C. demersum.

Subst Abus. 2006 Dec; 27(4): 63-7
Cheong R, Wilson RK, Cortese IC, Newman-Toker DE

Paradichlorobenzene (PDB) is a common household deodorant and pesticide found in room deodorizers, toilet bowl fresheners, and some mothballs. Although human exposure to the compound is generally limited and harmless, PDB in larger doses can produce neurotoxic effects, including a chemical "high" similar to that seen with inhalants such as toluene. Although rare, frank addiction to PDB has been reported, and, in such cases, has been associated with gait ataxia, tremor, dysarthria, limb weakness, and bradyphrenia, in various combinations. In such cases, the adverse neurologic consequences have been presumed to result from a direct toxic effect of this small, organic molecule. We report a case of chronic mothball ingestion where profound encephalopathy with cognitive, pyramidal, extrapyramidal, and cerebellar features appears to have been largely the result of PDB withdrawal, rather than direct toxicity. This case raises important questions about the mechanism of PDB neurotoxicity and possible treatment options for PDB-addicted patients. We propose that in cases with clear clinical deterioration after abstinence, readministration and gradual taper of PDB might be considered a therapeutic option.

Chemosphere. 2007 Jan; 66(10): 1939-46
Adebusoye SA, Picardal FW, Ilori MO, Amund OO, Fuqua C, Grindle N

Two polychlorinated biphenyl (PCBs)-degrading bacteria were isolated by traditional enrichment technique from electrical transformer fluid (Askarel)-contaminated soils in Lagos, Nigeria. They were classified and identified as Enterobacter sp. SA-2 and Pseudomonas sp. SA-6 on the basis of 16S rRNA gene analysis, in addition to standard cultural and biochemical techniques. The strains were able to grow extensively on dichloro- and trichlorobenzenes. Although they failed to grow on tetrachlorobenzenes, monochloro- and dichlorobenzoic acids, they were able to utilize all monochlorobiphenyls, and some dichlorobiphenyls as sole sources of carbon and energy. The effect of incubation with axenic cultures on the degradation of 0.9 mM 1,4-Dichlorobenzene, 0.44 mM 1,2,3- and 0.43 mM 1,3,5-trichlorobenzene in mineral salts medium was studied. Approximately, 80-90% of these xenobiotics were degraded in 200 h, concomitant with cell increase of up to three orders of magnitude, while generation times ranged significantly (P<0.05) from 17-32 h. Catechol 1,2-dioxygenase and catechol 2,3-dioxygenase activities were detected in crude cell-free extracts of cultures pre-grown with benzoate, with the latter enzyme exhibiting a slightly higher activity (0.15-0.17 micromolmin(-1) mg of protein(-1)) with catechol, suggesting that the meta-cleavage pathway is the most readily available catabolic route in the SA strains. The wider substrate specificity of these tropical isolates may help in assessing natural detoxification processes and in designing bioremediation and bioaugmentation methods.

Nat Chem Biol. 2006 Jun; 2(6): 338-45
Kokel D, Li Y, Qin J, Xue D

Naphthalene (1) and para-dichlorobenzene (PDCB, 2), which are widely used as moth repellents and air fresheners, cause cancer in rodents and are potential human carcinogens. However, their mechanisms of action remain unclear. Here we describe a novel method for delivering and screening hydrophobic chemicals in C. elegans and apply this technique to investigate the ways in which naphthalene and PDCB may promote tumorigenesis in mammals. We show that naphthalene and PDCB inhibit apoptosis in C. elegans, a result that suggests a cellular mechanism by which these chemicals may promote the survival and proliferation of latent tumor cells. In addition, we find that a naphthalene metabolite directly inactivates caspases by oxidizing the active site cysteine residue; this suggests a molecular mechanism by which these chemicals suppress apoptosis. Naphthalene and PDCB are the first small-molecule apoptosis inhibitors identified in C. elegans. The power of C. elegans molecular genetics, in combination with the possibility of carrying out large-scale chemical screens in this organism, makes C. elegans an attractive and economic animal model for both toxicological studies and drug screens.

Environ Health Perspect. 2006 Mar; 114(3): 453-9
Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, Ashley DL

We assessed concurrent exposure to a mixture of > 50 environmental chemicals by measuring the chemicals or their metabolites in the blood of 43 ethnically diverse children (3-6 years of age) from a socioeconomically disadvantaged neighborhood in Minneapolis. Over a 2-year period, additional samples were collected every 6-12 months from as many children as possible. We analyzed blood samples for 11 volatile organic compounds (VOCs), 2 heavy metals (lead and mercury, 11 organochlorine (OC) pesticides or related compounds, and 30 polychlorinated biphenyl (PCB) congeners. The evidence suggests that numerous VOCs originated from common sources, as did many PCBs. Longitudinal measurements indicate that between-child variance was greater than within-child variance for two VOCs (benzene, toluene), for both heavy metals (Pb, Hg), for all detectable OC pesticides, and for 15 of the measured PCB congeners (74, 99, 101, 118, 138-158, 146, 153, 156, 170, 178, 180, 187, 189, 194, 195). Despite the relatively small sample size, highest measured blood levels of 1,4-Dichlorobenzene, styrene, m-/p-xylene, Pb, Hg, heptachlor epoxide, oxychlordane, dichlorodiphenyldichloroethene (p,p -DDE), trans-nonachlor, and PCB congeners 74, 99, 105, 118, 138, 146, 153, 156, 170, and 180 were comparable with or higher than 95th percentile measurements of older children and adults from national surveys. Results demonstrate that cumulative exposures to multiple environmental carcinogens and neurotoxins can be comparatively high for children from a poor inner-city neighborhood.