In this study, we investigated the effect of organosulfur compounds including, diallyl sulfide (DAS), garlic extract, and dially disulfide (DADS) on inducible expression of UDP-glucuronosyltransferase (UGT1) and thyroid hormone level in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats. We measured UGT1 gene expression in rat liver and lung tissues after treatments. We found that a correlation was found to exist between UGT1 gene expression and active T-4 concentrations. The total concentration of plasma T-4 decreased in TCDD-alone treated male and female rats compared to control animals (TCDD-alone < control). Plasma T-4 concentration in TCDD + DAS, TCDD + garlic extract and TCDD + DADS treated groups were moderately higher than in TCDD alone animals, but lower than control animals. TCDD + DAS, TCDD + garlic extract and TCDD + DADS moderately increased T-4 glucuronidation and moderately reduced total T-4. The nonthyroidal nature of thyroid hormone reduction observed in this study extends the evidence for microsomal enzyme inducers as indirect thyroid tumor promoters in rats. Furthermore, the results of present study suggest protective effects of DAS, garlic extract, or DADS on TCDD-induced changes.
Animals ; Carcinogens ; Female ; Garlic ; Gene Expression ; Humans ; Liver ; Lung ; Male ; Plasma ; Rats* ; Tetrachlorodibenzodioxin ; Thyroid Gland*

On histological examination, an epidermolytic hyperkeratosis was observed adjacent to follicular papules on the back of a 53-year-old man. It has been reported that incidental epidermolytic hyperkeratosis occur either within various lesion (epidermal neoplasm, melanocytic neoplasm, scars, and inflammatory conditions) or in the normal skin adjacent to the lesion. This patient participated in the Vietnam War for 2 years, and had had contact with defoliants. He was treated for multiple peripheral neuropathies and cerebral infarcts. In keratinocytes, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; Agent Orange) contained in defoliating agents is associated with altered patterns of keratinocyte differentiation. So, as a cause of incidental epidermolytic hyperkeratosis, defoliant contact could be suspected.
Cicatrix ; Humans ; Hyperkeratosis, Epidermolytic* ; Keratinocytes ; Middle Aged ; Peripheral Nervous System Diseases ; Skin* ; Tetrachlorodibenzodioxin ; Veterans* ; Vietnam*

OBJECTIVES: In an epidemiologic study on the health impact of Agent Orange exposure, the valid estimation of exposure level is the most important step. Based on recent studies, we examined the correlation between exposure levels categorized by personal exposure estimates and serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD, Dioxin), exploring the possibility of utilizing the exposure level as a surrogate for the estimate of exposure to agent orange. METHODS: During the study period (Jan 1996-Feb 1996), blood specimens of 745 subjects taken randomly among 1,329 persons and kept frozen, were analyzed for 2,3,7,8-TCDD and six other dioxin congeners. The serum dioxin and congeners were measured in 1998 by CDC ,adjusted for serum lipids. We categorized the total exposure scores into five groups based on Agent Orange exposure data collected by interview and military records. Pearson and Spearman's correlation coefficients & multiple regression analysis were used to identify the relationship of the exposure level categorized with serum concentration of 2,3,7,8-TCDD, and six other dioxin congeners. RESULTS: Dioxin and the other congeners, except 1,2,4,6,7,8-HpCDD, showed significant correlations to exposure categories (p<0.005); 2,3,7,8-TCDD and OCDD showed positive correlations, whereas the other congeners did negative. The values of 2,3,7,8-TCDD differed according to exposure category and proportionally increased from the low exposure group to the high, a dose-response relationship, even after other possible confounding variables were adjusted for. In multiple regression analysis, age(beta=0.033), dioxin(beta=0.433), 1,2,3,7,8-PeCDD(beta=0.998), 1,2,3,4,7,8-HxCDD(beta=0.773), 1,2,3,6,7,8-HxCDD(beta=0.255), 1,2,3,7,8,9-HxCDD(beta=3.468), 1,2,3,4,6,7,8-HpCDD(beta=0.109) were found to be significantly related to the total exposure score(p<0.005). CONCLUSION: This study demonstrated that the use of such categorizations as a surrogate measure of agent orange exposure in identifying exposure degrees in a health impact study is valid.
Centers for Disease Control and Prevention (U.S.) ; Citrus sinensis* ; Confounding Factors (Epidemiology) ; Humans ; Military Personnel ; Tetrachlorodibenzodioxin ; Veterans* ; Vietnam*

A novel exonuclease protection mediated PCR assay (EPM-PCR) to detect the interaction of protein and DNA at a dioxin-responsive enhancer (DRE) upstream of the CYP1A1 gene in rat hepatic cytosol was established. A double-stranded DNA fragment containing two binding sites was designed and incubated with the aryl hydrocarbon receptor (AhR) transformed by 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) to generate TCDD: AhR: DNA complex which could protect receptor-binding DNA against exonuclease II (Exo III) digestion. With Exo III treatment, free DNAs were digested and receptor-bound DNAs remained that could be amplified by PCR. By agarose gel electrophoreses a clear band (285bp) was detected using TCDD-treated sample, while nothing with control samples. To detect transformed AhR-DRE complex, 2 fmol DNAs and 3 ug cytosol proteins were found to be sufficient in the experiment. Compared with gel retardation assay, this new method is more sensitive for monitoring the Ah receptor-enhancer interaction without radioactive pollution.
Binding Sites ; Cytochrome P-450 CYP1A1/*genetics ; Cytosol/metabolism ; DNA-Binding Proteins/chemistry ; Exodeoxyribonucleases/chemistry ; Liver/*metabolism ; Polymerase Chain Reaction ; Rats, Sprague-Dawley ; Receptors, Aryl Hydrocarbon/*chemistry ; Tetrachlorodibenzodioxin/*analogs & derivatives ; Tetrachlorodibenzodioxin/chemistry

General information is summarized, that is necessary to introduce a scientific assessment of the human health and exposure issue concerning dioxin and dioxin-like compound. Scientific literatures were reviewed to assess the background exposures to the dioxin-like compounds for normal residents. Epidemiologic studies were also reviewed to assess malignant and nonmalignant effects of dioxins. In 1997, the International Agency for Research on Cancer classified 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) as a human carcinogen, primarily based on occupational cohort studies. The US Environmental Protection Agency made the same decision in it's Draft Dioxin Reassessment. Epidemiologic evidences point to a generalized excess of all cancers, without any pronounced excess at specific sites. Reported non-cancer effects included a range of conditions affecting most systems. Among them, chloracne, elevation in gamma glutamyl transferase (GGT), and alterations in reproductive hormones are related to TCDD. Other adverse outcomes, such as lipid concentrations, diabetes, circulatory and heart diseases, immunologic disorders, neurobehavioral effects, and developmental outcomes require further study before their respective relationships to TCDD can be more definitively assessed.
Chloracne ; Cohort Studies ; Dioxins* ; Epidemiologic Studies ; Heart Diseases ; Humans* ; International Agencies ; Tetrachlorodibenzodioxin ; Transferases ; United States Environmental Protection Agency

BACKGROUND: TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a material of agent orange, was reported as a deadly poison in spite of its presence at extremely small doses. It has been reported that TCDD can cause various kinds of cancers and harmful effects on humans. However, a correlation between exposure to TCDD and cardiovascular disease is not yet known. Thus, we intended to examine the correlation between TCDD exposure and cardiovascular disease through an analysis of coronary angiograms in veterans of the Vietnam War. METHODS: A consecutive 115 patients undergoing coronary angiograms between April 2004 and June 2005 at Gwangju Veterans Hospital were analyzed. The patients were divided into two groups: 57 patients exposed to TCDD (Group I, average age 59.2+/-4.2 years) and 58 patients that were not exposed to TCDD (Group II, Average age 60.1+/-5.6 years). The clinical and coronary angiographic findings were evaluated. RESULTS: Baseline clinical characteristics, inflammatory markers and echocardiographic parameters were not different between patients in the two groups. The incidence of diabetes (43.9% vs. 25.0%, p=0.035) and hyperlipidemia (47.4% vs. 27.6%, p=0.028) were higher in group I patients than group II patients. Significant coronary artery stenosis was more common in group I (45 cases, 78.9%) thanin group II (33 cases, 56.9%) (p=0.011). CONCLUSIONS: There was a higher incidence of diabetes, hyperlipidemia, and significant coronary artery stenosis in patients that underwent a diagnostic coronary angiogram that were previously exposed to TCDD.
Angioplasty ; Cardiovascular Diseases* ; Citrus sinensis* ; Coronary Disease ; Coronary Stenosis ; Echocardiography ; Gwangju ; Hospitals, Veterans ; Humans ; Hyperlipidemias ; Incidence ; Tetrachlorodibenzodioxin ; Veterans* ; Vietnam*

This study was conducted in order to investigate the effects of Artemisia capillaris (AC) extract on disorders of hepatic functions and lipid metabolism induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disrupter, using male rats (SD, five weeks old) for a period of three weeks. These 37 animals were divided into four groups. AC extract was added as 1.5% or 3% levels to basal diets, respectively. TCDD (40 ug/kg B.W) was administered by intraperitoneal injection into rats after a week from the beginning of the experiment. AC extract alleviated the increase of rat's relative liver weights induced by TCDD. Thymuses of all rats treated with TCDD were apparently shrunken by approximately 80%. Levels of white blood cells (WBC), red blood cells, hemoglobin, and hematocrits were significantly increased by treatment with TCDD, however, WBC tended to decrease by AC extract diets. In hepatic function, the elevation of glutamic oxalacetic transaminase activities by TCDD treatment was diminished by AC extract diets. Serum HDL-cholesterol levels were significantly elevated by AC extract diets. The apparent increase of triglyceride levels of rat livers induced by TCDD was significantly suppressed in the AC extract diet groups. Hepatic cytosolic catalase activities significantly decreased by treatment with TCDD showed a recovering trend by AC extract diets. In histochemical observation, the fat droplets and apoptosis of hepatocytes treated with TCDD were markedly alleviated by AC extract diets. These results indicated that AC could exert recovering effects on some disorders of hepatic functions, lipids metabolism, and antioxidant activities resulting from TCDD treatment.
Animals ; Apoptosis ; Artemisia ; Catalase ; Cytosol ; Diet ; Erythrocytes ; Hematocrit ; Hemoglobins ; Hepatocytes ; Humans ; Injections, Intraperitoneal ; Leukocytes ; Lipid Metabolism ; Liver ; Male ; Rats ; Tetrachlorodibenzodioxin ; Thymus Gland ; Weights and Measures

A defoliant is a toxic chemical agent used to remove leaves. Defoliants are classified into 6 types (purple, pink, green, blue, white and orange). From 1962 to 1971, due to removing leaves and securing their ability to see, the U.S. Army Chemical Corps veterans handled and sprayed defoliant in Vietnam. This resulted in exposure to Agent Orange and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). This agent induces many medical problems in humans. Since 1992 in Korea, exposure to defoliants have given rise to several problems. However, there were few reactions due to the lack of data, social apathy, and international relationships. In this article, we review characteristics and diseases related to defoliants.
2,4,5-Trichlorophenoxyacetic Acid ; 2,4-Dichlorophenoxyacetic Acid ; Apathy ; Citrus sinensis ; European Continental Ancestry Group ; Humans ; Korea ; Skin ; Skin Diseases ; Tetrachlorodibenzodioxin ; Veterans ; Vietnam

Merkel cell carcinoma is a rare aggressive primary skin cancer which mostly occurs in the elderly on sun-exposed skin. It usually presents as a solitary dome-shaped red or purple nodule on the head, neck and extremities. The mortality rate is higher than the rate for malignant melanoma because its local recurrence is common. Agent Orange, an herbicide widely used as a defoliant in the Vietnam War, contains dioxin contaminants and can cause several dermatoses and skin cancers. We report a case of multiple Merkel cell carcinoma in a 65-year-old male with lesions on the head and neck, who had been exposed to Agent Orange during Vietnam War.
2,4,5-Trichlorophenoxyacetic Acid ; 2,4-Dichlorophenoxyacetic Acid ; Aged ; Carcinoma, Merkel Cell ; Citrus sinensis ; Extremities ; Head ; Humans ; Male ; Melanoma ; Neck ; Recurrence ; Skin ; Skin Diseases ; Skin Neoplasms ; Tetrachlorodibenzodioxin ; Veterans ; Vietnam

Glucose is a key fuel and an important metabolic substrate in mammals. A number of mechanisms contribute to the changes in cellular functions that occur in response to exposure of endogenous factors. These include increased cytokines and growth factors as well as the glucose specific effects due to increased intracellular level of glucose. The kidneys play a major role in the regulation of plasma glucose levels, and ever increasing attention is now being given to renal glucose transporters as the implications including diabetes mellitus. The primary rabbit renal proximal tubule cells (PTCs) culture system utilized in my study has well recognized to retain in vitro the differentiated phenotype typical of the renal proximal tubule, including a polarized morphology and distinctive proximal tubule transport. Thus, I examined the effects of several factors on Na+/glucose cotransporters in PTCs. ANG II, EGF, epinephrine, TCDD, high glucose, bee venom, partially inhibited [14C]-alpha-methyl-D-glucopyranoside (alpha-MG) uptake, whereas BSA stimulates alpha-MG uptake in PTCs. On the other hand, caffeic acid, ginsenosides, and estrogens protected oxidative stress-induced inhibition of alpha-MG uptake.
Bee Venoms ; Blood Glucose ; Cytokines ; Diabetes Mellitus ; Epidermal Growth Factor ; Epinephrine ; Estrogens ; Ginsenosides ; Glucose ; Hand ; Intercellular Signaling Peptides and Proteins ; Kidney ; Mammals ; Phenotype ; Tetrachlorodibenzodioxin