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PubMed1998

Role of oxidant stress and antioxidant protection in acephate-induced renal tubular cytotoxicity.

Acephate (AT) is an organophosphate (OP) insecticide. Due to their reputation for low environmental persistence, OP pesticides are often used indiscriminately resulting in detrimental exposure to humans and other nontarget species. Although the toxicity of OP compounds is primarily through blockade of neural transmission via inhibition of acetylcholinesterase, studies have revealed histopathological alterations in the renal proximal tubules, suggesting a role for additional mechanisms in renal toxicity. It is our hypothesis that Reactive Oxygen Species (ROS) may play a role in OP-induced renal tubular injury for the following reasoning. Renal tubular cells concentrate many nephrotoxic chemicals including OPs, and renal injury from many of these compounds has been shown to arise from excessive ROS production. Furthermore, it has been established that many phosphorothiolates, which are sulfur-containing OPs and constitute the class of OP compounds to which AT belongs, are S-oxidized to highly reactive intermediates within cells and tissues. Because of these considerations, we examined whether ROS play a role in OP-induced renal tubular epithelial cell (LLC-PK1) toxicity using AT as a prototype. AT produced a concentration- and time-dependent increase in cell damage in LLC-PK1 cells, measured by lactate dehydrogenase (LDH, % of total) leakage. The cytotoxicity (LDH) induced by 2500 ppm of AT over 72 h was significantly suppressed by antioxidants 2-methylaminochroman (2-MAC) and desferrioxamine (DFO). H2O2 levels were significantly elevated following exposure of LLC-PK1 cells to 2500 ppm of AT. Malondialdehyde (MDA) formation was also significantly increased in AT-exposed cells compared to the control cells, indicating the occurrence of enhanced lipid peroxidation. 2-MAC and DFO, in addition to providing cytoprotection, inhibited AT-induced MDA generation in a significant and concentration-dependent manner. Results from this study, which is the first to explore the toxic effects of AT on renal tubular cells, demonstrate that toxic action of AT on kidney cells is partly through an ROS-mediated mechanism. Based on these direct in vitro findings, we further hypothesize that oxidant stress may play a role in the pathogenesis of AT-induced acute tubular necrosis and renal dysfunction observed in cases of AT overdoses.

Animals↗

PubMed1987

Dose-response of promotion by polychlorinated biphenyls and chloroform in rat liver foci bioassay.

Using the rat liver foci bioassay a dose-response relationship was evaluated for the promoting activity of the ubiquitous and persistent environmental pollutants polychlorinated biphenyls (PCBs) and chloroform. Initiation of liver foci was performed by oral administration of a single dose of 8 mg/kg body wt of diethylnitrosamine to weanling female Sprague-Dawley rats. For polychlorinated biphenyls (PCBs) and chloroform a dose-dependent promoting effect was found. The lowest effective dose of PCBs was 1 mg/kg body wt, given three times a week for 11 consecutive weeks. That of chloroform was 100 mg/kg body wt, administered twice a week for 11 consecutive weeks. The livers were screened for preneoplastic foci 12 weeks after starting the experiments. The amounts of PCBs as well as chloroform normally taken up by humans are greater than a factor of 1000 lower than the effective experimental doses. Thus the risk of human exposure to these chemicals is estimated to be very low. In the case of heavy pollution with PCBs, however, as happened in the yusho accident (Japan, 1968), the daily intake of PCBs was in the range of the effective doses used in the experiment.

Adenosine Triphosphatases↗

PubMed2001

Behavioral effects induced by acute exposure to benzo(a)pyrene in F-344 rats.

Polycyclic aromatic hydrocarbons (PAHs) are highly persistent environmental pollutants which pose potential adverse effects on human health. Benzo(a)-pyrene (B(a)P) is the prototypical representative of these widely dispersed lipophylic contaminants. (B(a)P) exposure in experimental animals results in an array of tissue- and organ-specific responses including carcinogenicity, teratogenicity, reproductive and immunotoxicity. However, no previous studies have examined the potential neurobehavioral toxicity of B(a)P in vivo. The present study was conducted to investigate the behavioral effects induced by single oral doses of (B(a)P) in 8-week-old male and female F-344 rats. Rats were exposed to 0, 12.5, 25, 50, 100 and 200 mg/kg of B(a)P by oral gavage. Motor activity measurements and the functional observational battery (FOB) were used to assess behavioral changes induced by B(a)P at 2, 4, 6, 8, 10, 12, 24, 48, 72 and 96 h post treatment. Statistical analyses revealed significant (p <0.001) dose, sex and time interactions. (B(a)P) doses ranging from 25 to 200 mg/kg produced a significant suppression (up to 60%) in four motor activity parameters: horizontal activity, total distance, stereotype and vertical activity in both sexes within 2 and 4h of dosing. B(a)P treated male and female animals also showed significant (p <0.001) changes in neuromuscular, autonomic, sensorimotor and physiological functions within 2 and 4h post B(a)P administration except in the 12.5 mg/kg treatment group. The 12.5 mg/kg dose did not produce significant (p > 0.05) behavioral toxicity in either males or females. All treated animals (25-200 mg/kg) recovered from the toxic effects of B(a)P by 72 h. Significant (p < 0.05) gender differences were noted in FOB test measures with males displaying greater sensitivity to B(a)P. These data suggest that motor activity and FOB measurements can be used as indices to detect B(a)P neurotoxicity.

Journal Article↗

PubMed2003

Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach.

Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative response of the organism to stimulate gluconeogenesis. They showed for the first time that HCB causes impairment of the gluconeogenic pathway. Therefore, the reduced levels of glucose would thus be the consequence of decreased gluconeogenesis, enhanced glucose storage, and unaffected glycolysis. The impairment of gluconeogenesis (especially for PEPCK) and the related variation in glucose levels caused by HCB treatment could be a consequence of the oxidative stress produced by the fungicide. Tryptophan adds its effect to this decrease in the higher phases of HCB intoxication, where its levels overcome the control values possibly owing to the drastic decline of URO-D. This derangement of carbohydrates leads porphyric hepatocytes to have lower levels of free glucose. These results contribute to our understanding of the protective and modulatory effect that diets rich in carbohydrates have in hepatic porphyria disease.

Animals↗

PubMed1999

Relative distribution of polychlorinated biphenyls among tissues of neonatal American alligators (Alligator mississippiensis).

Recent papers have investigated the utility of chemical analysis of the chorioallantoic membrane (CAM) as a nonlethal indicator of avian and reptilian exposure to persistent environmental contaminants. This study was undertaken to evaluate the chemical distribution among fat, CAM, and residual yolk tissues of live neonatal American alligators (Alligator mississippiensis) to investigate the potential utility of CAM use as a nonlethal indicator of exposure to polychlorinated biphenyls (PCBs). CAMs were collected from neonatal alligators at hatch, whereas yolk sacs and fat tissues were taken from each animal at euthanization (3 weeks posthatch). All collected tissue samples were separately Soxhlet extracted and analyzed by GC/ECD for PCBs. Log normalized, individual PCB congener concentrations in CAMs were significantly correlated with concentrations in fat (r(2) = 0.62) and yolk (r(2) = 0.56) tissues. Coefficients of determination from comparisons of homologue group concentrations varied from 0.13 to 0.90. Residue levels in neonatal oviparous organism tissues may be qualitatively assessed through chemical analyses of CAM tissues removed from discarded eggshells.

Allantois↗

PubMed2000

Enzymology of Phanerochaete chrysosporium with respect to the degradation of recalcitrant compounds and xenobiotics.

The archetypal white-rot fungus Phanerochaete chrysosporium has been shown to degrade a variety of persistent environmental pollutants. Many of the enzymes responsible for pollutant degradation, which are normally involved in the degradation of wood, are extracellular. Thus, P. chrysosporium is able to degrade toxic or insoluble chemicals more efficiently than other microorganisms. P. chrysosporium has a range of oxidative and reductive mechanisms and uses highly reactive, nonspecific redox mediators which increase the number of chemicals that can be effectively degraded. This review gives an overview of the enzymes that are believed to be important for bioremediation and briefly discusses the degradation of some individual chemicals.

Biodegradation, Environmental↗

PubMed2026

Genomic Insights into Mammaliicoccus sciuri from Subclinical Bovine Mastitis to Unveil Key Resistance, Virulence, Biofilm and Adaptation Traits.

The Mammaliicoccus sciuri (M. sciuri), is recognized as a reservoir of antimicrobial resistance (AMR) genes, poses challenges in the Indian dairy sector where antibiotic use is poorly regulated. This study aimed to genomically characterize M. sciuri (formerly Staphylococcus sciuri) isolates recovered from subclinical mastitis (SCM) cattle milk. A total of 128 composite (quarter-wise pooled) milk samples were collected from 199 households (HH) across 16 epiunits /villages in four blocks of Chikkaballapur district, Karnataka, India. Of these, 36 milk samples (28.13%, 36/128; 95% CI: 21.06–36.46%) were diagnosed with SCM using the California Mastitis Test (CMT) and bacteriological culture yielded 113 isolates (88.28%; 113/128; 95% CI: 81.56–92.77%) were phenotypically identified as Staph spp. Through molecular technique PCR targeting the gap gene, two isolates (1.77%; 2/113; 95% CI: 0.49–6.22%) from Hosuru and Gattamaranahalli epiunits were confirmed as M. sciuri and both isolates were mecA-positives indicating methicillin resistance. Whole genome sequencing (WGS) identified 36–37 resistance genes (mecA and blaZ), conferring resistance to β-lactams, macrolides, fluoroquinolones and aminoglycosides. Horizontal gene transfer (HGT) was evidenced by diverse mobile genetic elements (MGEs) such as SCCmec variants, insertion sequences, transposons (IS3, IS6, IS256, and IS1182) and plasmids (Rep1, Rep13, RepUS5 and RepUS43). Virulence profiling uncovered biofilm-associated genes (ica, bap) and heavy metal resistance operons (ars, cop, znu) suggesting mechanisms for environmental persistence and co-selection of resistance traits. Phylogenetic analysis of 99 global isolates revealed host-and geography-specific clustering with Indian isolates occupying distinct evolutionary niches. These findings highlights its possible role as an AMR reservoir and also in bovine mastitis.

Animals↗

PubMed2025

Unlocking microbial potential: advances in omics and bioinformatics for aromatic hydrocarbon degradation.

Aromatic hydrocarbons (AHs) are persistent environmental pollutants with high toxicity. Bacterial degradation of AHs provides a sustainable and cost-effective approach for the remediation of sites contaminated with both mono- and polycyclic aromatic hydrocarbons. Aerobic degradation of AHs typically involves oxygenases-mediated hydroxylation followed by aromatic ring cleavage. In contrast, anaerobic degradation relies on diverse activation mechanisms that ultimately converge on the central intermediate benzoyl-CoA. Over the past decades, research on bacterial degradation of AHs has grown steadily, supported by advances in omics and bioinformatics. In this review, we summarize the current knowledge on the pathways, enzymes, and microbial diversity involved in AH degradation, highlighting how omics and bioinformatic approaches are advancing our understanding of this process. However, to improve our knowledge of microbial AHs catabolism, it is crucial to prioritize the characterization of novel enzymes and pathways, especially those mediating anaerobic and hybrid degradation strategies. Addressing this gap requires the development of specialized resources that incorporate a broader taxonomic diversity and an expanded inventory of anaerobic genes and enzymes supported by experimental evidence. Equally important is the integration of multi-omics technologies, artificial intelligence, and ecological modeling into unified analytical pipelines. These efforts will be key to fully unlocking microbial metabolic potential and guiding more effective bioremediation and monitoring strategies for AHs.

Biodegradation, Environmental↗

PubMed1988

Metabolic activation and toxicity of a DDT-metabolite, 3-methylsulphonyl-DDE, in the adrenal zona fasciculata in mice.

Whole-body autoradiography of 14C-labelled 3-methylsulphonyl-DDE (3-MeSO2-DDE) in female C57BL mice revealed a heavy accumulation in the adrenal cortex. Fairly high radioactivity appeared in the nasal mucosa and fat, while the labelling of the liver was intermediate. The adrenal radioactivity remained largely unextracted in tissue-sections treated with organic solvents. In the liver and intestinal contents the radioactivity was partly extracted, whereas in all other tissues almost completely extracted. According to light microscopic autoradiography, the tissue-bound adrenal radioactivity was confined to the zona fasciculata, leaving the other adrenal zones devoid of bound material. Incubation of 3-MeSO2-DDE with adrenal tissue (300 X g supernatant) revealed a dose- and time-dependent covalent binding to protein and formation of water-soluble metabolites. The cytochrome P-450 inhibitors metyrapone and carbon monoxide inhibited both covalent binding and polar metabolite formation. Addition of reduced glutathione decreased binding, while polar metabolite formation was increased. Histopathological examination of adrenals from 3-MeSO2-DDE-treated mice revealed extensive vacuolation and necrosis of the zona fasciculata 1-12 days after single doses down to 25 mg/kg. Degenerative changes were observed at 12.5 mg/kg. In contrast to 3-MeSO2-DDE, 14C-labelled 3,3'-bis(methylsulphonyl)-DDE was not accumulated in the adrenal cortex. 3-MeSO2-DDE is thus a persistent environmental pollutant with a unique ability to produce acute toxicity subsequent to metabolic activation in a mammalian tissue.

Adrenal Cortex↗

PubMed1981

Activation of phenanthrene to mutagenic metabolites and evidence for at least two different activation pathways.

Phenanthrene, generally considered to be a non-carcinogen, was converted by mammalian tissue preparations to products that were mutagenic for Salmonella typhimurium TA100 and TA1537. In TA100 the mutagenic response was highly dependent on the activation system used. High amounts of 9000 x g supernatant fraction from the liver of rats induced by Aroclor 1254 were required. Equivalent amounts of microsomal or cytosolic fraction alone did not activate phenanthrene to an observable extent. Furthermore, this activation was only observed when the rats had been treated with Aroclor. Liver preparations from control rats and from rats treated with phenobarbital, beta-naphthoflavone, a mixture of both, and transstilbene oxide failed to activate phenanthrene to mutagens for TA100. Interestingly, liver microsomes and 9000 x g supernatant fractions of Aroclor-treated mice also failed significantly to activate phenanthrene to mutagens for this strain. Addition of pure epoxide hydrolase to the S9 mix had no influence on this activation. Glutathione (GSH) decreased the mutagenicity, but uridine diphosphate glucuronic acid (UDPGA) had only minor effects. An adenosine-3'-phosphate-5'-sulfate phosphate (PAPS) generating system, however, increased the number of his+ revertants from TA100 (2.7-fold). TA1537 was reverted by mutagens produced from phenanthrene by liver microsomes or 9000 x g supernatant fraction, when the microsomal epoxide hydrolase was inhibited by 1,1,1-trichloropropene oxide. This activation pathway exists in Aroclor-treated rats and mice. The results show that at least 2 different pathways for metabolic activation of phenanthrene exist which were observed in 2 differentially sensitive tester strains and distinguished by their different metabolic requirements. Furthermore, the study shows that earlier suggestions do not hold that equivalent results can be obtained by inducing animals with a combination of phenobarbital and beta-naphthoflavone instead of the environmentally persistent Aroclor 1254. Moreover, the study provides a striking example that the use of 9000 x g supernatant in amounts corresponding to standard practice but sub-optimal for a particular compound only impede the detection of a weak mutagen and that the rapid inactivation of active metabolites by inactivating enzymes may be responsible for negative results in mutagenicity testing.

Animals↗

PubMed1989

TCDD alters medial epithelial cell differentiation during palatogenesis.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widely distributed, persistent environmental contaminant that is teratogenic in mice, where it induces hydronephrosis and cleft palate. The incidence of clefting has been shown to be dose dependent after exposure on either gestation Day (GD) 10 or 12, although the embryo is more susceptible on GD 12. TCDD-exposed palatal shelves meet but do not fuse, and programmed cell death of the medial epithelial cells is inhibited. The mechanism of action through which TCDD alters the program of medial cell development has not been examined in earlier studies, and it is not known whether the mechanism is the same regardless of the dose or developmental stage of exposure. In this study, C57BL/6N mice, a strain sensitive to TCDD, were dosed orally on GD 10 or 12 with 0, 6, 12, 24, or 30 micrograms/kg body wt, in 10 ml corn oil/kg. Embryonic palatal shelves were examined on GD 14, 15, or 16. The degree of palatal closure, epithelial surface morphology, and cellular ultrastructure, the incorporation of [3H]TdR, the expression of EGF receptors, and the binding of 125I-EGF were assessed. After exposure on GD 10 or 12, TCDD altered the differentiation pathway of the medial epithelial cells. The palatal shelves were of normal size and overall morphology, but fusion of the medial epithelia of the opposing shelves did not occur. TCDD prevented programmed cell death of the medial peridermal cells. The expression of EGF receptors by medial cells continued through Day 16 and the receptors were able to bind ligand. The medial cells differentiated into a stratified, squamous, keratinizing epithelium. The shift in phenotype to an oral-like epithelium occurred after exposure on either GD 10 or 12. At the lower dose (6 micrograms/kg), fewer cleft palates were produced, but those shelves which did respond had a fully expressed shift in differentiation. Whether the exposure begins on GD 10 or 12 or whether the dosing level produces only a few cleft palates within a litter, TCDD produced cleft palate by altering the differentiation program of the medial cells.

Administration, Oral↗

PubMed1991

Differential DNA-protein crosslinking in lymphocytes and liver following chronic drinking water exposure of rats to potassium chromate.

Carcinogenic chromium (VI) compounds are persistent environmental contaminants with potential for human exposure through drinking water. One lesion associated with chromium (VI) exposure is the formation of DNA-protein crosslinks (DPC). In an attempt to develop markers of chromium exposure, the formation of DPC in lymphocytes was investigated. Fisher 344 rats were exposed to K2CrO4 in their drinking water for 3 and 6 weeks at concentrations of 100 and 200 ppm chromium. No DPC could be detected in isolated splenic lymphocytes using the alkaline elution technique or by using a polyclonal antibody to chromate-induced DPC. However, increased complexing of proteins with DNA was demonstrated in liver following 3 weeks of exposure at both 100 and 200 ppm chromium. Intraperitoneal administration of potassium chromate did not induce detectable DPC in lymphocytes; however, an increased association of proteins with isolated DNA was detected in the liver. DPC were also induced in isolated splenic lymphocytes following a 2-hr exposure in vitro to 100 microM K2CrO4 in a salts-glucose medium. Although chromium was detected in blood, liver, and kidney, blood levels were comparatively much lower. A comparison of chromium levels required to induce DPC in lymphocytes in vitro and the amount absorbed orally suggests that the white blood cell chromium levels following oral exposure may be too low to induce measurable DNA-protein crosslinks in lymphocytes.

Animals↗

PubMed1989

Hematotoxic effects in the rat of a toluene dinitro derivative after short-term exposure.

3,5-Dinitro-4-chloro-alpha,alpha,alpha-trifluorotoluene (DNCTT) is an intermediate in the synthesis of dinitroaniline herbicides and was involved in an episode of ground water pollution in 1977. The compound presents a high environmental persistence, which may have possible implications concerning public health. In one experiment male Sprague-Dawley rats were administered DNCTT for 3 days at a dose level of 150 mg/kg body wt by oral gavage. Groups of rats were sacrificed up to 10 days after the end of the administration, at 2-day intervals. Methemoglobin was increased up to Day 7; white blood cells were also increased both in peripheral blood and in bone marrow smears. Spleen relative weights were observed to increase slightly at Days 7 and 10; microscopic examination revealed marked congestion with an increased density of the spleen's white pulp. In a similar scheduled experiment, but at a dose level of 300 mg/kg body wt, the bone marrow white cell series were not affected initially, but were affected after 3 days at the end of the administration. DNCTT has a definite effect on white cells.

Animals↗

PubMed1988

Evaluation of the immunotoxicity of beta-hexachlorocyclohexane (beta-HCH).

beta-HCH, an isomeric contaminant formed during the manufacture of the insecticide lindane, is a persistent environmental and food chain pollutant which has been reported to exhibit estrogenic activity in rodents and in fish. To investigate potential toxic effects on the reproductive and immune systems, beta-HCH was fed to female B6C3F1 mice for 30 days. Mice exposed to 0, 100, or 300 mg of beta-HCH/kg of diet were evaluated for changes in ovarian and uterine histology, body weight, lymphoid organ weight and histology, splenic cellularity, antigen-specific IgM and IgG plaque-forming cells (PFC), proliferative responses to mitogens, natural killer (NK) cell activity, and induction of cytolytic T lymphocytes. The ovaries and endometrial epithelium exhibited normal architecture. No alterations were observed in body weight, lymphoid organ weight and histology, or splenic cellularity whereas significant changes were found in several immune functions at the 300 mg/kg dose. Proliferation of splenocytes to the mitogens LPS, PHA, and Con A was decreased by 39, 43, and 57%, respectively. T-lymphocyte-mediated cytolysis of tumor targets was decreased by 25% with a concurrent reduction of 45% in NK activity. There was no significant reduction in the number of IgM or IgG PFC in exposed animals. These data indicate that beta-HCH causes nonestrogenic immune function changes in the adult mouse without gross changes in lymphoid organ weight, histology, or cellularity.

Animals↗

PubMed1986

Evaluation of acute bioassays for assessing toxicity of polychlorinated biphenyl-contaminated soils.

Proposed State of California regulations use fish toxicity information as one criterion in municipal or industrial waste hazard evaluation. Static 96-hr bioassays were performed using fathead minnows (Pimephales promelas), blacksmith (Chromis punctipinnis), and glass shrimp (Palaemonetes kadiakensis) exposed to soil experimentally contaminated with up to 500 ppm polychlorinated biphenyl (PCB) capacitor fluid added at a concentration of 500 mg liter-1. Other bioassays were conducted with a 6-day mixing period prior to the bioassay or with acetone added to solubilize the PCBs. No mortality attributable to PCB toxicity was observed in definitive bioassays using the two fish and one invertebrate species. PCB levels leached from soil containing 500 ppm Aroclor 1242 ranged from less than 0.6 to 3.4 ppb in freshwater tests to 3.5 ppb in seawater bioassays. Using these data as the basis for waste classification, soils contaminated with up to 500 ppb PCBs during capacitor spills would be designated nonhazardous. PCBs are known to be environmentally persistent and to bioaccumulate. Acute toxicity tests, therefore, do not adequately evaluate the general toxicity of PCB-contaminated soils. Hazardous waste regulations for hydrophobic compounds such as PCBs should instead be based upon chronic toxicity data and should also consider bioaccumulation potential.

Animals↗

PubMed1993

Estimating the risks of liver and lung cancer in humans exposed to trichloroethylene using a physiological model.

Trichloroethylene (TCE) is a common and persistent environmental contaminant found in groundwater near most large cities and at Superfund landfill sites. In many cases, the groundwater is the primary source for water consumption. Because of the widespread distribution of TCE in the environment, a significant fraction of the population may ingest or inhale TCE over an extended period of time. Typically, environmental concentrations of TCE are in the ppb range. Health concerns for environmental exposure to TCE stem largely from positive outcomes in laboratory cancer bioassay studies with rodents at relatively high exposure concentrations. Epidemiological evidence that TCE is a human carcinogen is equivocal.

Animals↗

PubMed2004

Mixing of perfluorinated carboxylic acids with dipalmitoylphosphatidylcholine.

Perfluorinated acids are emerging as an important class of persistent environmental pollutant, thus raising human health concerns. To understand the behavior of these compounds in biological systems, the mixing behavior of two perfluorinated acids, perfluorododecanoic and perfluorotetradecanoic acid, with dipalmitoylphosphatidylcholine (DPPC) was studied in monolayers at the air-water interface and in fully hydrated DPPC bilayers. The mixing behavior of both acids was indicative of an attractive interaction and partial miscibility with DPPC at the air-water interface. In the bilayer studies, the fluorinated acids cause peak broadening and elimination of the pretransition of DPPC. The onset temperature of the main phase transition remains constant in the presence of the fluorinated acids suggesting immiscibilities in the gel phase. Below X(DPPC) = 0.97 significant peak broadening of the main phase transition can be observed. These results suggest strong interaction between the respective acid and DPPC, and that both acids are able to partition into the lipid bilayer. However, their mixing behavior is far from ideal, thus suggesting the presence of domains or lipid aggregates with high acid concentrations which may (adversely) impact the function of biological mono- and bilayers.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2004

Antioxidants regulate normal human keratinocyte differentiation.

Cancer begins with a normal cell that, due to persistent environmental insult, is transformed, via a series of progressively more insidious steps, into a cancer cell. A major goal of chemopreventive therapy is to alter the normal cell response to the environmental agent with the goal of inhibiting disease progression. (-)-Epigallocatechin-3-gallate (EGCG) is an important bioactive green tea antioxidant that possesses remarkable cancer chemopreventive properties. We have recently explored the hypothesis that EGCG prevents cancer by promoting keratinocyte differentiation. Based on our findings, we argue that EGCG acts to enhance the differentiation of normal keratinocytes. This is a potentially important finding, as it represents a novel mechanism of disease inhibition by EGCG--cancer preventive "differentiation therapy". However, not all antioxidant chemopreventive agents work by this mechanism. Curcumin, for example, inhibits the differentiation-promoting activity of EGCG. This report discusses the mechanism of EGCG and curcumin action in regulating expression of involucrin, a marker of keratinocyte differentiation.

Anticarcinogenic Agents↗