Intestinal T lymphocytes of different rat strains in immunotoxicity.
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In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytes, an inventory was made of single and organized lymphocytes in the epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 344, and Lewis rats. The single and organized lymphocytes were examined microscopically. In addition, the single lymphocytes in the epithelium (IEL) and lamina propria (LPL) were analyzed by flow cytometry. Next, the use of flow cytometry analysis was explored to detect changes in the IEL T-lymphocyte population in subacute oral studies with the immunomodulating agents azathioprine and hexachlorobenzene. Untreated random-bred Wistar rats exhibited a large interindividual variability in IEL composition, while the variability was small in inbred Fischer 344 and Lewis rats. The explorative study with the 2 model immunomodulating compounds demonstrated that hexachlorobenzene increased the number of intraepithelial T lymphocytes with CD8+ phenotype at the cost of T cells with CD4+ phenotype in Lewis rats. Azathioprine did not induce distinct effects on the percentages of IEL. The data indicate that the intraepithelial lymphocytes in the intestines are a potential target for orally administered immunomodulating compounds and should therefore receive more attention in toxicologic pathology studies. (+info)
Environmental exposure to hexachlorobenzene (HCB) and risk of female breast cancer in Connecticut.
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Earlier studies have provided inconclusive results relating hexachlorobenzene (HCB), an organochlorine fungicide, to female breast cancer risk. The current study, with a total of 304 breast cancer cases and 186 controls recruited in Connecticut between 1994 and 1997, examined the association by directly comparing breast adipose tissue levels of HCB between incident breast cancer cases and noncancer controls. The cases and controls were patients who had breast biopsies or surgery at the Yale-New Haven Hospital (New Haven, CT) and histologically diagnosed either as breast cancer or benign breast disease. Information on major known or suspected risk factors for breast cancer was obtained through in-person interview by trained interviewers. No significant difference in mean breast adipose tissue levels of HCB was observed between breast cancer patients (21.0 ppb) and controls (19.1 ppb) in this large case-control study. The risk also did not vary significantly by menopausal status, estrogen or progesterone receptor status of the breast cancer cases, breast cancer histology, stage of diagnosis, or type of benign breast disease. Among parous women who reported ever breast feeding, an odds ratio (OR) of 0.5 [95% confidence interval (CI), 0.2-1.4] was observed when the highest quartile was compared with the lowest quartile. However, no association was observed among parous women who reported never breast feeding (OR = 0.7; 95% CI, 0.3-1.7 for the fourth quartile). For nulliparous women, the adjusted OR was 2.1 (95% CI, 0.5-8.8) for the third tertile when compared with the lowest based on few subjects. Therefore, our study does not support a positive association between environmental exposure to HCB and risk of breast cancer. (+info)
Organochlorine in the serum of inhabitants living near an electrochemical factory.
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OBJECTIVES: To measure the impact of occupational and lifestyle factors on concentrations of organochlorine compounds in a general population sample living near an electrochemical factory with a high airborne concentration of hexachlorobenzene (HCB). METHODS: Serum samples from 608 people (328 selected from a random sample) were collected in 1994. Information on lifestyles, occupation, and medical condition was obtained by questionnaire. RESULTS: HCB and polychlorinated biphenyls (PCBs) were detected in all samples (means 36.7 ng/ml and 4.3 ng/ml respectively), followed by dichlorodiphenyl dichloroethane (DDE) and beta-hexachlorocyclohexane (beta-HCH), found in 98.7% and 87.3% of the samples respectively (means 4.6 ng/ml and 2.5 ng/ml, respectively). Concentrations of HCB were the highest ever reported. Occupation in the factory was the main determinant of the variation in concentrations of HCB (regression coefficients 1.52 (SEM 0.14) in 1n (HCB) for workers in the production department, and 2.13 (0.23) for workers in maintenance department) and explained the highest concentrations of HCB found in men of middle age. In retired workers, concentrations of HCB declined with time since retirement. The PCBs, dichlorodiphenyl trichloroethane (DDT), and beta-HCH were independent of the occupation and concentrations were similar to those found in other populations. Concentrations of beta-HCH and DDE in the whole population, and HCB among non-workers, were higher in women than in men. Concentrations of all measured organochlorine compounds increased with age and body mass index. Consumption of locally caught fish was an independent determinant of HCB and PCB concentrations. CONCLUSIONS: This population incorporated HCB directly through occupation in the electrochemical factory, by airborne pollution, and consumption of locally caught fish. Concentrations of other common organochlorine compounds were not higher than expected. Environmental exposures to these compounds deserve attention due to their persistence and potential health effects. (+info)
The role of the immune system in hexachlorobenzene-induced toxicity.
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Hexachlorobenzene (HCB) is a persistent environmental pollutant. The toxicity of HCB has been extensively studied after an accidental human poisoning in Turkey and more recently it has been shown that HCB has immunotoxic properties in laboratory animals and probably also in man. Oral exposure of rats to HCB showed stimulatory effects on spleen and lymph node weights and histology, increased serum IgM levels, and an enhancement of several parameters of immune function. Moreover, more recent studies indicate that HCB-induced effects in the rat may be related to autoimmunity. In Wistar rats exposed to HCB, IgM antibodies against several autoantigens were elevated; in the Lewis rat, HCB differently modulated two experimental models of autoimmune disease. Oral exposure of rats to HCB induces skin and lung pathology in the rat. Recently several studies have been conducted to investigate whether these skin and lung lesions can be related to HCB-induced immunomodulation, and these studies will be discussed in this review. HCB-induced skin and lung lesions probably have a different etiology; pronounced strain differences and correlation of skin lesions with immune parameters suggest a specific involvement of the immune system in HCB-induced skin lesions. The induction of lung lesions by HCB was thymus independent. Thymus-dependent T cells were not likely to be required for the induction of skin lesions, although T cells enhanced the rate of induction and the progression of the skin lesions. No deposition of autoantibodies was observed in nonlesional or lesional skin of HCB-treated rats. Therefore, we concluded that it is unlikely that the mechanism by which most allergic or autoimmunogenic chemicals work, i.e., by binding to macromolecules of the body and subsequent T- and B-cell activation, is involved in the HCB-induced immunopathology in the rat. Such a thymus-independent immunopathology is remarkable, as HCB strongly modulates T-cell-mediated immune parameters. This points at a very complex mechanism and possible involvement of multiple factors in the immunopathology of HCB. (+info)
Comparative hepatocarcinogenicity of hexachlorobenzene, pentachlorobenzene, 1,2,4,5-tetrachlorobenzene, and 1,4-dichlorobenzene: application of a medium-term liver focus bioassay and molecular and cellular indices.
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Of the twelve different chlorobenzene isomers, a thorough evaluation of carcinogenicity has only been assessed on monochlorobenzene, 1,2-, and 1,4-dichlorobenzene, and hexachlorobenzene. In the studies presented here, we measured the ability of 1,4-dichlorobenzene (DCB), 1,2,4,5-tetrachlorobenzene (TeCB), pentachlorobenzene (PeCB), and hexachlorobenzene (HCB) to promote glutathione S-transferase pi (GSTP1-1) positive preneoplastic foci formation in rat liver, following diethylnitrosamine (DEN) initiation. The results from these studies show that TeCB, PeCB, and HCB all promote the formation of GSTP1-1 positive foci and that DCB does not. The numbers and area of foci were greatest following HCB promotion, and TeCB and PeCB were approximately equal in their promoting ability. Levels of hepatic CYP1A2, CYP2B1/2, non-focal GSTP1-1, and c-fos were measured in response to treatment with the 4 chlorobenzene isomers, as were reduced glutathione (GSH) and oxidized glutathione (GSSG) levels. Results from these studies show that induction of CYP1A2 and CYP2B1/2 have correlation with both the presence and degree of GSTP1-1 foci promotion by the 4 chlorobenzenes. Alterations in GSH and GSSG levels were similar in PeCB- and TeCB-treated animals in that GSSG levels were significantly decreased, whereas HCB and DCB did not have this effect, although HCB treatment led to a significant increase in GSH levels. We conclude that induction of CYP1A2 or CYP2B1/2 by chlorobenzene isomers may indicate promotional ability, and that this property might be exploited to predict the hepatocarcinogenicity of other chlorobenzene isomers. (+info)
Susceptibility to infections and immune status in Inuit infants exposed to organochlorines.
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We investigated whether organochlorine exposure is associated with the incidence of infectious diseases in Inuit infants from Nunavik (Arctic Quebec, Canada). We compiled the number of infectious disease episodes during the first year of life for 98 breast-fed and 73 bottle-fed infants. Concentrations of organochlorines were measured in early breast milk samples and used as surrogates to prenatal exposure levels. Immune system parameters were determined in venous blood samples collected from infants at 3, 7, and 12 months of age. Otitis media was the most frequent disease, with 80. 0% of breast-fed and 81.3% of bottle-fed infants experiencing at least one episode during the first year of life. During the second follow-up period, the risk of otitis media increased with prenatal exposure to p,p'-DDE, hexachlorobenzene, and dieldrin. The relative risk (RR) for 4- to 7-month-old infants in the highest tertile of p, p'-DDE exposure as compared to infants in the lowest tertile was 1. 87 [95% confidence interval (CI), 1.07-3.26]. The RR of otitis media over the entire first year of life also increased with prenatal exposure to p,p'-DDE (RR, 1.52; CI, 1.05-2.22) and hexachlorobenzene (RR, 1.49; CI, 1.10-2.03). Furthermore, the RR of recurrent otitis media ( [Greater/equal to] 3 episodes) increased with prenatal exposure to these compounds. No clinically relevant differences were noted between breast-fed and bottle-fed infants with regard to immunologic parameters, and prenatal organochlorine exposure was not associated with immunologic parameters. We conclude that prenatal organochlorine exposure could be a risk factor for acute otitis media in Inuit infants. (+info)
Serum concentrations of hexachlorobenzene in family members of workers in an electrochemical factory.
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OBJECTIVES: This study analyzed the effect of living in the same household with a worker employed in an electrochemical factory on the hexachlorobenzene (HCB) concentrations of serum in the general population of Flix, Spain. METHODS: A total of 608 subjects from the general population (response rate 42%) completed a questionnaire about residence, occupation, life-styles, and medical history and provided blood samples. Among them, 412 had never worked in the electrochemical factory. Information about the occupation of the family members was completed, and the subjects were classified with the degree of relationship with the worker having been taken into account. A multiple linear regression analysis was conducted to model HCB serum for nonfactory workers. RESULTS: Having a spouse who worked in the factory was associated with elevated HCB concentrations in serum. The adjusted relative increases were 1.28 (P=0.0004) and 1.23 (P=0.0022) times the corresponding value of people not living with workers of the factory, respectively for spouses of current and past workers. Relatives other than spouses did not show any increase. CONCLUSIONS: The results of this study suggest that, among nonworkers, living with a worker of the electrochemical factory in Flix is associated with an increase in concentrations of HCB in blood. These findings may suggest a source of exposure to HCB that has thus far not been studied and that could be important in populations not occupationally exposed to organochlorines. (+info)
Excretion of hexachlorobenzene and metabolites in feces in a highly exposed human population.
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A set of 53 individuals from a population highly exposed to airborne hexachlorobenzene (HCB) were selected to study the elimination kinetics of this chemical in humans. The volunteers provided blood, 24-hr urine, and feces samples for analysis of HCB and metabolites. The serum HCB concentrations ranged from 2.4 to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this human population has the highest HCB blood levels ever reported. All analyzed feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/- 629). The HCB concentration in feces strongly correlated with HCB in serum (r = 0.85; p < 0.001), suggesting an equilibrium in feces/serum that is compatible with a main pulmonary entrance of the chemical and low intestinal excretion of nonabsorbed foodborne HCB. The equilibrium is also compatible with a nonbiliary passive transfer of the chemical to the intestinal lumen. Two HCB main metabolites, pentachlorophenol (PCP) and pentachlorobenzenethiol (PCBT), were detected in 51% and 54% of feces samples, respectively. All urine samples contained PCP and PCBT, confirming the conclusions of a previous study [Environ Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed that whereas daily urinary elimination of metabolites may account for 3% of total HCB in blood, intestinal excretion of unchanged HCB may account for about 6%, thus showing the importance of metabolism in the overall elimination of HCB. The elimination of HCB and metabolites by both routes, however, appears to be very small (< 0.05%/day) as compared to the estimated HCB adipose depots. Features of HCB kinetics that we present in this study, i.e., nonsaturated intestinal elimination of HCB and excretion in feces and urine of inert glutathione derivatives, may explain, in part, the absence of porphyria cutanea in this human population heavily exposed to HCB. (+info)