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*

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*

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

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*

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

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

PURPOSE: We previously reported that Panax ginseng water extract (PG-WE) played both preventive and therapeutic roles on testicular toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in animal study, one of the most potent environmental pollutants. Thus we investigated whether PG-WE might be useful in the treatment of male infertility, because men in modern society are exposed by numerous environmental hormones. MATERIALS AND METHODS: Eighteen patients with abnormal semen analysis and 8 volunteers whose semen analysis were normal as control group were enrolled in this study. Before PG-WE administration, semen analysis, hormonal study, liver and renal function test, CBC, and urinalysis were checked in all subjects. PG-WE (2.4 gm) was administered everyday for 8 weeks in both groups. Follow-up semen analysis and laboratory studies were checked at 13th week. RESULTS: In patient group semen volume was increased (2.4 1.3 ml vs 2.6 1.6 ml, p=0.051). Semen volume as well as sperm concentration in oligospermia patient were increased but not significantly. Serum estradiol level decreased by PG-WE treatment in patient group (p=0.005). All subjects showed no toxic effect. CONCLUSIONS: Our data suggest that Panax ginseng is a potential agent that can improve abnormal sperm parameters in infertile male patients and also improve the sperm quality in healthy men.
Animals ; Environmental Pollutants ; Estradiol ; Follow-Up Studies ; Humans ; Infertility ; Infertility, Male* ; Liver ; Male ; Male* ; Oligospermia ; Panax* ; Semen ; Semen Analysis ; Spermatozoa ; Tetrachlorodibenzodioxin ; Urinalysis ; Volunteers ; Water*

BACKGROUND: Panax ginseng is known to decrease the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular toxicity. Thus, we aimed to reveal the differences between Panax ginseng and Panax quinquefolium extract for their effects on TCDD-induced toxicity. METHODS: Forty rats were divided into four groups; the control group, the TCDD only group, the TCDD plus Panax ginseng group, and the TCDD plus Panax quinquefolium-treated groups. Ginseng extract was given orally to rats from day one to twenty-one. TCDD was intraperitoneally administered to rats at a single dose of 50 microgram/kg on the seventh day. The pathologic changes were then examined. The changes of body weight, cholesterol and GOT in the serum were also examined. RESULTS: The TCDD toxicity was prominent in the thymus, liver and testis. The thymus showed atrophy and an inverse pattern of lymphocyte density in the cortex and medulla. The liver revealed central necrosis with fatty changes. On electron microscopy, the seminiferous tubules showed destruction of the spermatogonia, clear spaces or vacuolar changes and degeneration in the Sertoli cells or germ cells. The above mentioned TCDD-induced changes were reduced in the rats that were administered with Panax ginseng, whereas Panax quinquefolium did not reduce these changes. CONCLUSION: The protective effects of Panax ginseng on the TCDD-induced toxicity were more effective than those of Panax quinquefolium.
Animals ; Atrophy ; Body Weight ; Cholesterol ; Germ Cells ; Humans ; Liver ; Lymphocytes ; Male* ; Microscopy, Electron ; Necrosis ; Panax* ; Rats* ; Seminiferous Tubules ; Sertoli Cells ; Spermatogonia ; Testis ; Tetrachlorodibenzodioxin ; Thymus Gland

PURPOSE: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most potent environmental pollutants, is known to disrupt the endocrine, immune, and reproductive system. This study was carried out to investigate the effect of a panax ginseng water extract (PG-WE) on the survival rate, sperm quality, and fertility impaired by TCDD. MATERIALS AND METHODS: Eighty male guinea pigs were divided into 8 groups. The normal control group received the vehicle and saline. TCDD was intraperitoneally injected at a single dose of 1microgram/kg. A PG-WE was administered at 100 or 200mg/kg/ day 1wk prior to (P groups) or subsequent to (C groups) TCDD-exposure for 12 and 10 weeks, respectively. The G groups received the vehicle and the PG-WE of 100 or 200mg/kg/day, respectively. The parameters for the male guinea pigs were assessed for 40 weeks. The effects on the F1 generation were assessed at a growth period of F1. RESULTS: All single TCDD-treated group animals died within 18 days and the survival rate of the PG-WE-treated groups increased in a dose dependant manner. Forty to 70% of the P and C groups survived until the 40th week and reached sexual maturation. The death rate of the progeny born from the PG-WE-treated groups was significantly lower than that in the NC group (14.3%). The M/F ratio of the F1 generation in the P and C groups had higher female birth ratio. The sperm number and morphology showed no significant differences among the groups. The PG-WE increased the sperm motility in the guinea pigs exposed to TCDD. CONCLUSIONS: Panax ginseng is a useful agent that can neutralize endocrine disrupters and environmental pollutants, and help maintain a high sperm quality after a growth period.
Animals ; Environmental Pollutants ; Female ; Fertility ; Guinea Pigs* ; Guinea* ; Humans ; Male ; Mortality ; Panax* ; Parturition ; Pregnancy* ; Sexual Maturation ; Sperm Count ; Sperm Motility ; Spermatozoa* ; Survival Rate ; Tetrachlorodibenzodioxin* ; Water