Evidence for induction of apoptosis in T cells from murine fetal thymus following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes thymic atrophy, but the precise mechanism of such toxicity remains unresolved. The current study investigated the role of apoptosis in TCDD-induced thymic involution following perinatal exposure to TCDD. To this end, C57BL/6 pregnant mice were injected intraperitoneally on gestational day (GD) 14 with a single dose of 10 microg/kg TCDD. Analysis of the thymus on GDs 15, 16, 17, and 18, and on postnatal day (PD) 1, showed a remarkable reduction in thymic cellularity 3-7 days post-TCDD exposure. TCDD treatment also caused marked changes in the proportions of T-cell subsets, particularly on GD 17 and GD 18 thymocytes. In vitro culture of thymocytes from mice exposed perinatally to TCDD showed increased apoptosis when compared to the controls, which peaked on day 3 post-TCDD exposure. Triple-color staining showed that TCDD induced apoptosis in all four subpopulations of T cells, with the double-positive T cells undergoing the highest level. Moreover, increased cleavage of caspase-3 was seen when TCDD-exposed GD 17 thymocytes were directly tested. Furthermore, apoptosis-associated phenotypic changes were found in thymocytes of mice perinatally exposed to TCDD, characterized by an increase in expression of CD3, alphabetaTCR, IL-2R, and CD44, and a decrease in CD4, CD8, and J11d markers. Finally, thymocytes from mice exposed perinatally to TCDD showed higher levels of Fas, TRAIL, and DR5 mRNA, but the levels of Bcl-2, Bcl-xL, and Bax were either unaltered or changed moderately. Taken together, these results suggest that TCDD-induced thymic atrophy following perinatal exposure may result, at least in part, from increased apoptosis mediated by death receptor pathway involving Fas, TRAIL, and DR5.     

Immunotoxicity: the risk is real.

Several papers published over the last year represent significant progress in closing the gap between rodent immunotoxicity data and human risk and indicate that, at least for the developing immune system, the concern raised by rodent data is justified. The studies reviewed here show that suppression of immune responses in rodents is predictive of suppression of immune responses in humans and that there is a relationship between immune suppression following developmental exposure to the toxicants and enhanced risk of infectious or neoplastic disease in humans. The three cases highlighted here are remarkable in that they all deal with real-world environmental exposures that represent different media -- air (cigarette smoke), water (arsenic), and food (polychlorinated biphenyls [PCBs]) -- and constitute very real risks. Moreover, the arsenic and PCB studies actually demonstrate a quantitative relationship between human exposure and immune suppression. There is evidence that in utero exposure to cigarette smoke and arsenic but not PCBs is associated with increased risk of allergic disease as well. There is clearly potential for designing studies that could address both issues.     

Anticholinesterase Mechanism as a Factor of Immunotoxicity of Various Chemical Compounds

Experiments on Wistar rats showed that acute poisoning with chemicals in a dose of 0.75 LD₅₀ (dimethyl dichlorovinyl phosphate, sarin, VX substance, sulfur yperite, lewisite, tetraethyl lead, dichloroethane) inhibiting platelet acetylcholine esterase, -naphthyl-AS-acetate esterase, and -naphthyl-butyrate esterase suppressed T cell-mediated immune reactions.     

Utility of a routine medical surveillance program with benzene exposed workers

BACKGROUND: A medical surveillance program of benzene-exposed workers has to be established in such a way as to observe early signs of benzene-induced cytopenia, pancytopenia, or leukemia. This study evaluates the utility of routine medical survey applied to benzene-exposed workers by analyzing the hematological, immunological, and cytogenetic assay results. METHODS: The results of a previous study of hematological, immunological, and cytogenetic assays in benzene-exposed workers (up to 15 ppm) are used to discuss medical surveillance program by defining the relationship between various benzene exposure concentrations and toxic endpoints. RESULTS: Exposure to benzene concentration lower than 5 ppm does not produce any abnormal hematological measurements. For benzene cumulative exposure above 100 (ppm-years), some blood indices [mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), band neutrophils] show significant differences in comparison to the control group. The incidence of dicentric chromosomes was higher and the level of B-lymphocytes was lower even with workers exposed to 5 ppm of benzene; correlation with exposure indicators was not found. CONCLUSIONS: The results suggest that peripheral blood indices, although not sensitive enough, are still the most suitable parameters in a health surveillance program applied to benzene-exposed workers. B-lymphocytes could be a promising indicator of the benzene-induced damage. Cytogenetic tests did not prove to be suitable. Further investigation of useful screening tests for health surveillance program of benzene-exposed workers is still required.     

胸腺在免疫毒性病理学评价中的作用和意义

胸腺是中枢性淋巴器官，无须抗原的刺激T淋巴细胞在皮质自主地进行分化和成熟，这是免疫系统正常功能发育的重要组成部分。当暴露于免疫毒性物质和内源性糖皮质激素时，胸腺是敏感的靶器官，胸腺的大小或重量出现明显的降低，这往往是化合物或药物导致的敏感的皮质胸腺细胞改变最初观测到的指标。因此，胸腺组织病理学和重量的改变与免疫毒性的筛选具有特定的关联，对胸腺的病理学评价在免疫毒性研究中具有重要作用和意义。文中从胸腺生理和毒性病理学的角度对其作用和研究意义进行综述。     

Assessment of mercury exposure and malaria in a Brazilian Amazon riverine community

Small-scale gold mining in the Brazilian Amazon occurs in areas with high rates of malaria transmission. Amazonian populations can be exposed to mercury through direct contact with the mining process and/or through fish consumption. Because of data from experimental studies, we examined the potential for mercury to affect host response to malaria. A cross-sectional survey was done in Jacareacanga, a riverine community in Para state, in a region of intense alluvial gold mining. A sample of 205 persons was selected by cluster sampling from the total population of approximately 2000. A brief medical history and exam were conducted, malaria slides were obtained, and hair samples were taken to measure mercury levels. The average hair mercury level was 8.6 micrograms/g, ranging from 0.3 to 83.2 micrograms/g. The most important predictors of elevated mercury levels were high fish consumption and low income. Although there was no prevalent malaria, the odds of reporting a past malaria infection was four times higher for those also reporting a history of working with mercury.     

8:2 Fluorotelomer alcohol causes immunotoxicity and liver injury in adult male C57BL/6 mice

8:2 Fluorotelomer alcohol (8:2 FTOH) is widely used in houseware and industrial goods and is ubiquitous in the surrounding environment. 8:2 FTOH has been linked to hepatoxicity, nephrotoxicity, and reproductive toxicity, as well as endocrine‐disrupting effects. However, as of yet, the research regarding immunotoxicity of 8:2 FTOH remains largely limited. In the present study, adult male C57BL/6 mice were administered with 10, 30, and 100 mg/kg/d 8:2 FTOH by gavage for 28 days to investigate its immunotoxicity in vivo. The results showed that exposure to 8:2 FTOH caused increases in liver weight and histological changes in the liver, including vacuolation, cell swelling, immune cell infiltration, karyopyknosis and nuclear swelling. No histological change in either the spleen or the thymus was observed after administration of 8:2 FTOH. In addition, exposure to 8:2 FTOH reduced the concentration of IL‐1β in serum, and mRNA levels of IL‐1β, IL‐6, and TNF‐α in both the thymus and spleen. CXCL‐1 mRNA expression was downregulated in both the liver and thymus after 8:2 FTOH administration, while only IL‐1β mRNA expression was upregulated in the liver. Moreover, the exposure of primary cultured splenocytes to 8:2 FTOH inhibited the ConA‐stimulated proliferation of splenocytes at concentrations of 30 and 100 μM, and the LPS‐stimulated proliferation of splenocytes at 100 μM. Furthermore, 8:2 FTOH inhibited the level of secreted IFN‐γ in ConA‐stimulated splenocytes. The results obtained in the study demonstrated that 8:2 FTOH posed potential immunotoxicity and liver injury in mice. Our findings will provide novel data for the health risk assessment of 8:2 FTOH.