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The function of Cytochrome (CYP) P450 in plants to enhance detoxification of herbicide metabolism is well-known. However, the knowledge of gene quantification for detecting and detoxifying pollutants and other toxicants by an indigenous plant growing in a contaminated site is limited. The objective of this research is to evaluate the potential of detecting or degrading 2,3,7,8 Tetrachlorodibenzodioxin (TCDD) in soil using a native plant growing in a contaminated site via the gene expression of Cytochrome P450 monooxygenases (P450s) method. The novelty of this research is that P450s in native plants possibly acts as a bioindicator on contaminated land by increasing its gene expression levels induced by the presence of TCDD. In seedling toxicity test and cytochrome enzyme activity test, a significant difference in the root length (range of value: 580.2–799.2 mm) and enzyme activity (range of value: 31.2–82.3 nmolmin −1  g −1 total protein) of such indigenous plant was found in 10 µg/L TCDD treatment when compared to other treatments. 13- and 20-fold levels of gene expression in CYP71C1 and CYP79A61 of the plant growing in a contaminated site were found after 10 µg/L TCDD treatment. The results revealed that such indigenous plant is sensitive to the detection of such persistent organic pollutant in the field site and involves gene expression change facilitated by a plant‒microbe symbiotic association. The current findings can provide an insight to use another option for pollution monitoring using non-standard plant models. Highlights CYP71C1 and CYP79A61 induction by TCDD. CYP450 is sensitive to detect trace amount of TCDD. Applicable to TCDD detection.

Background: A single in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestation day 15 decreased epididymal sperm count in adult rats and thus was used to establish a tolerable daily intake for TCDD. However, several laboratories have been unable to replicate these findings. Moreover, conflicting reports of TCDD effects on daily sperm production suggest that spermatogenesis may not be as sensitive to the adverse effects of TCDD as previously thought. Data sources: We performed a PubMed search using relevant search terms linking dioxin exposure with adverse effects on reproduction and spermatogenesis. Data synthesis: Developmental exposure to TCDD is consistently linked with decreased cauda epididymal sperm counts in animal studies, although at higher dose levels than those used in some earlier studies. However, the evidence linking in utero TCDD exposure and spermatogenesis is not convincing. Conclusions: Animal studies provide clear evidence of an adverse effect of in utero TCDD exposure on epididymal sperm count but do not support the conclusion that spermatogenesis is adversely affected. The mechanisms underlying decreased epididymal sperm count are unknown; however, we postulate that epididymal function is the key target for the adverse effects of TCDD.

Hydroxy-substituted tetrachlorodibenzo[b,e][1,4]dioxin and tetrachlorodibenzo[b,d]furans have been synthesized using 3,4-dichloroanisole, 2,3,6-trichlorophenol and 4,5-dichlorocatechol as starting materials and electrophilic and/or nucleophilic aromatic substitution reactions for the assembly of the dibenzo[b,e][1,4]dioxin and dibenzo[b,d]furan systems. The thus-obtained phenolic compounds were then alkylated with N-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde)-protected 3-bromopropan-1-amine to give the corresponding N-Dde protected 3-aminopropoxy-substituted tetrachlorodibenzo[b,e][1,4]dioxin and tetrachlorodibenzo[b,d]furans, respectively. Hydrazinolysis-mediated Dde removal from the former compound provided the corresponding amino-substituted dioxin, which was coupled to carboxy-substituted magnetic beads affording magnetic beads coated by the amino-substituted dioxin. The latter is an attractive intermediate for the development of selective single-standard DNA (ssDNA) aptamers, which constitute molecular recognition elements in photonic biosensors with potential application to the monitoring of the dangerous environmental pollutants, dioxins having serious implications in human health.

As a consequence of ubiquitous use of brominated organic chemicals, there is a concern for persistent or increasing environmental levels of polybrominated dibenzo‐p‐dioxins/furans (PBDD/Fs) and mixed polychlorinated and polybrominated di‐benzo‐p‐dioxins/furans (PXDD/Fs). Hence, there is a need to broaden the toxicological and environmental knowledge about these compounds, as a basis for risk assessment. In the study presented here, the relative potencies (REPs) for 18 PBDD/F and PXDD/F congeners were determined in four dioxin‐specific bioassays from different species: dioxin receptor chemically activated luciferase expression assay (DR‐CALUX, rat hepatoma cells), TV101L (human hepatoma cells), and GPC.2D (guinea pig adenoma cells), as well as ethoxyresorufin‐O‐deethylase induction in the fish cell line RTL‐W1 (rainbow trout liver cells). The bioassay specific REP factors presented here enable the assessment of the contribution from PBDD/Fs and PXDD/Fs to total 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) equivalents (TEQs: toxic equivalents), using bioassay analysis. The PBDD/Fs were found to be equally potent as their chlorinated analogues in the three mammalian assays, whereas the PXDD/Fs showed relatively higher potencies. Of special concern were the 2,3,7,8‐substituted penta‐ and tetrahalogenated congeners, for which mean REPs were >1. The 2‐B‐1,3,7,8‐CDD (2‐bromo‐1,3,7,8‐tetrachlorodibenzo‐p‐dioxin) was up to three times more potent than TCDD in individual experiments (on weight basis). The RTL‐W1 was less sensitive to the tested compounds with overall 10‐fold lower REPs than the mammalian cell lines. Although the REP factors exhibited species‐specific differences, overall resembling rank orders of dioxin‐like potency were obtained.

For both type 1 and type 2 diabetes mellitus, the rates have been increasing in the United States and elsewhere; rates vary widely by country, and genetic factors account for less than half of new cases. These observations suggest environmental factors cause both type 1 and type 2 diabetes. Occupational exposures have been associated with increased risk of diabetes. In addition, recent data suggest that toxic substances in the environment, other than infectious agents or exposures that stimulate an immune response, are associated with the occurrence of these diseases. We reviewed the epidemiologic data that addressed whether environmental contaminants might cause type 1 or type 2 diabetes. For type 1 diabetes, higher intake of nitrates, nitrites, and N-nitroso compounds, as well as higher serum levels of polychlorinated biphenyls have been associated with increased risk. Overall, however, the data were limited or inconsistent. With respect to type 2 diabetes, data on arsenic and 2,3,7,8-tetrachlorodibenzo-p-dioxin relative to risk were suggestive of a direct association but were inconclusive. The occupational data suggested that more data on exposure to N-nitroso compounds, arsenic, dioxins, talc, and straight oil machining fluids in relation to diabetes would be useful. Although environmental factors other than contaminants may account for the majority of type 1 and type 2 diabetes, the etiologic role of several contaminants and occupational exposures deserves further study.

This study is a consequence of a distinct fish decline in the Danube river since the beginning of the 1990s. In contrast to the decline of fish population, former studies have repeatedly documented that the water quality along the Danube river is improving. However, the conclusion of a pilot study in 2002 was that a high hazard potential is associated with local sediments. The present study documents that sediment samples from the Danube river showed comparatively high aryl hydrocarbon receptor mediated activity in biotests, using the cell lines GPC.2D.Luc, H4IIE (DR-CALUX®) and RTL-W1. The combination of chemical analysis, fractionation techniques and different in vitro tests revealed that priority pollutants could not explain the main induction, even though the concentrations of priority polycyclic aromatic hydrocarbons (PAHs) were very high (maximum in the tributary Schwarzach, sum of 16 EPA PAHs 26 μg/g). In conclusion, this investigation shows that nonpriority pollutants mainly mediate the high induction rates. Nevertheless, owing to the effects of PAHs towards fish and the connection between dioxin-like activity and carcinogenicity, the link between contamination and the fish population decline cannot be ruled out.

Background: One of the outcomes positively associated with dioxin exposure in humans is type 2 diabetes. Objectives: This study was conducted in order to find the molecular biological evidence for the diabetogenic action of dioxin in adipose samples from Vietnam veterans. Methods: We obtained 313 adipose tissue samples both from Vietnam veterans who were exposed to dioxin (Operation Ranch Hand) and from comparison veterans who served in Southeast Asia with no record of dioxin exposure. We conducted quantitative reverse-transcribed polymerase chain reaction studies on selected marker mRNAs from these samples. Results: We found the most sensitive and reliable molecular indicator of dioxin-induced diabetes to be the ratio of mRNA of glucose transporter 4 (GLUT4) and nuclear transcription factor kappa B (NFκB), a marker of inflammation. This ratio showed significant correlations to serum dioxin residues and to fasting glucose among those in the Ranch Hand group and, surprisingly, even in the comparison group, who have low levels of dioxin comparable to the general public. Such a correlation in the comparison group was particularly significant among those with known risk factors such as obesity and family history of diabetes. Conclusions: These results show that the GLUT4:NFκB ratio is a reliable marker for the diabetogenic action of dioxin, particularly at very low exposure levels that are not much higher than those found in the general public, implying a need to address current exposure levels.

Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals. Nearly 20 years after the Seveso, Italy, accident, we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones (n = 62) and in the surrounding noncontaminated area (n = 58). Plasma IgG levels decreased with increasing TCDD plasma concentration (r = -0.35, p = 0.0002). Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest (< 3.5 ppt) TCDD levels to 1,163 mg/dL in the group with the highest (20.1-89.9 ppt) TCDD levels (p = 0.002). The association was significant (p = 0.0004) after adjusting for age, sex, smoking, and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs. IgM, IgA, C3, and C4 plasma concentrations did not exhibit any consistent association with TCDD levels. We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components. The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse. Methodologic issues, results, and possible sources of variation between studies are discussed. The possible long-term immunologic effects of TCDD exhibited by the participants of the present study, coupled with the increased incidence of lymphatic tumors in the area of the accident, warrant further investigation.

From 1972 to 1982, approximately 1,500-2,100 US Air Force Reserve personnel trained and worked on C-123 aircraft that had formerly been used to spray herbicides in Vietnam as part of Operation Ranch Hand. After becoming aware that some of the aircraft on which they had worked had previously served this purpose, some of these AF Reservists applied to the US Department of Veterans Affairs (VA) for compensatory coverage under the Agent Orange Act of 1991. The Act provides health care and disability coverage for health conditions that have been deemed presumptively service-related for herbicide exposure during the Vietnam War. The VA denied the applications on the basis that these veterans were ineligible because as non-Vietnam-era veterans or as Vietnam-era veterans without \"boots on the ground\" service in Vietnam, they were not covered. However, with the knowledge that some air and wipe samples taken between 1979 and 2009 from some of the C-123s used in Operation Ranch Hand showed the presence of agent orange residues, representatives of the C-123 Veterans Association began a concerted effort to reverse VA's position and obtain coverage. At the request of the VA, Post-Vietnam Dioxin Exposure in Agent Orange-Contaminated C-123 Aircraft evaluates whether or not service in these C-123s could have plausibly resulted in exposures detrimental to the health of these Air Force Reservists. The Institute of Medicine assembled an expert committee to address this question qualitatively, but in a scientific and evidence-based fashion. This report evaluates the reliability of the available information for establishing exposure and addresses and places in context whether any documented residues represent potentially harmful exposure by characterizing the amounts available and the degree to which absorption might be expected. Post-Vietnam Dioxin Exposure rejects the idea that the dioxin residues detected on interior surfaces of the C-123s were immobile and effectively inaccessible to the Reservists as a source of exposure. Accordingly, this report states with confidence that the Air Force Reservists were exposed when working in the Operation Ranch Hand C-123s and so experienced some increase in their risk of a variety of adverse responses.

Dioxins are persistent organic pollutants interfering with endocrine systems and causing reproductive and developmental disorders. The objective of our project was to determine the impact of an in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive function of male and female offspring in the rat with a special emphasis on the immature period. We used a low dose of TCDD (unique exposure by oral gavage of 200 ng/kg at 15.5 days of gestation) in order to mirror a response to an environmental dose of TCDD not altering fertility of the progeny. We choose a global gene expression approach using Affymetrix microarray analysis, and testes of 5 days and ovaries of 14 days of age. Less than 1% of the expressed genes in gonads were altered following embryonic TCDD exposure; specifically, 113 genes in ovaries and 56 in testes with 7 genes common to both sex gonads. It included the repressor of the aryl hydrocarbon receptor (Ahrr), the chemokines Ccl5 and Cxcl4 previously shown to be regulated by dioxin in testis, Pgds2/Hpgds and 3 others uncharacterized. To validate and extend the microarray data we realized real-time PCR on gonads at various developmental periods of interest (from 3 to 25 days for ovaries, from 5 to the adult age for testes). Overall, our results evidenced that both sex gonads responded differently to TCDD exposure. For example, we observed induction of the canonic battery of TCDD-induced genes coding enzymes of the detoxifying machinery in ovaries aged of 3-14 days of age (except Cyp1a1 induced at 3-10 days) but not in testes of 5 days (except Ahrr). We also illustrated that inflammatory pathway is one pathway activated by TCDD in gonads. Finally, we identified several new genes targeted by TCDD including Fgf13 in testis and one gene, Ptgds2/Hpgds regulated in the two sex gonads.