Immunological Effects of Chlorinated Dibenzo-p-Dioxins

Kerkvliet, Nancy I.

doi:10.2307/3432722

Cited by 45 publications

(47 citation statements)

References 62 publications

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“…Accidental or occupational exposure as well as background exposure of the general population to PCBs and dioxins may affect the human immune system (7,8,(14)(15)(16)(17)(18). There is suggestive evidence that dioxin-like compounds influence the immune response by changing the CD4/CD8 ratio, the ratio of other lymphocyte populations, or the antibody production by B cells (4,7,8,15,16,18,19).…”

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confidence: 99%

“…Experiments in which laboratory animals and nonhuman primates have been exposed to PCDD/PCDFs and/or PCBs indicate that the immune system is perhaps the most sensitive target for PHAH-induced toxicity. Indeed, 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) causes cellular and humoral immune suppression, increased susceptibility to various infectious diseases, thymus atrophy, and depressed antibody and lymphoproliferative responses (6)(7)(8)(9)(10)(11). Moreover, in wildlife, PCBs/dioxins affect the survival of birds, seals, and beluga whales by diminishing host resistance and increasing incidence and severity of infections (12,13).…”

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confidence: 99%

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Immunologic biomarkers in relation to exposure markers of PCBs and dioxins in Flemish adolescents (Belgium).

Heuvel

Koppen

Staessen

et al. 2002

Environ Health Perspect

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In this study, we investigated 17- to 18-year-old boys and girls to determine whether changes in humoral or cellular immunity or respiratory complaints were related to blood serum levels of polychlorinated biphenyls (PCBs) and dioxin-like compounds after lifetime exposure in Flanders (Belgium). We obtained blood samples from and administered questionnaires to 200 adolescents recruited from a rural area and two urban suburbs. Physicians recorded medical history and respiratory diseases. We measured immunologic biomarkers such as differential blood cell counts, lymphocyte phenotypes, and serum immunoglobulins. As biomarkers of exposure, we determined the serum concentrations of PCBs (PCB 138, PCB 153, and PCB 180) and dioxin-like compounds [chemical-activated luciferase expression (CALUX) bioassay]. The percentages of eosinophils and natural killer cells in blood were negatively correlated with CALUX toxic equivalents (TEQs) in serum (p = 0.009 and p = 0.05, respectively). Increased serum CALUX TEQs resulted in an increase in serum IgA levels (p = 0.05). Furthermore, levels of specific IgEs (measured by radioallergosorbent tests) of cat dander, house dust mite, and grass pollen were also significantly and negatively associated with the CALUX TEQ, with odds ratios (ORs) equal to 0.63 [95% confidence interval (CI), 0.42-0.96], 0.68 (0.5-0.93), and 0.70 (0.52-0.95), respectively. In addition, reported allergies of the upper airways and past use of antiallergic drugs were negatively associated with CALUX TEQs, with ORs equal to 0.66 (0.47-0.93) and 0.58 (0.39-0.85), respectively. We found a negative association between IgGs and marker PCBs in serum (p = 0.009). This study shows that immunologic measurements and respiratory complaints in adolescents were associated with environmental exposure to polyhalogenated aromatic hydrocarbons (PHAHs). The negative correlation between PHAHs and allergic responses in adolescents suggested that exposure may entail alterations in the immune status.

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confidence: 99%

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confidence: 99%

Immunologic biomarkers in relation to exposure markers of PCBs and dioxins in Flemish adolescents (Belgium).

Heuvel

Koppen

Staessen

et al. 2002

Environ Health Perspect

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“…TCDD exposure during mouse embryogenesis causes craniofacial anomalies, such as cleft palate, and hydronephrosis (6), whereas in adult rodents, TCDD causes an elevated incidence of hepatic carcinoma and pulmonary and skin tumors (7)(8)(9). Other consequences of TCDD exposure include disturbances of lipid metabolism, cardiovascular and craniofacial abnormalities during fish development (10,11), and immunotoxic (12), reproductive, and endocrine effects (13)(14)(15)(16), some of which appear to be present also in exposed humans (17)(18)(19).…”

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confidence: 99%

Aromatic Hydrocarbon Receptor Interaction with the Retinoblastoma Protein Potentiates Repression of E2F-dependent Transcription and Cell Cycle Arrest

Puga

Barnes

Dalton

et al. 2000

Journal of Biological Chemistry

282

221

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Polyhalogenated aromatic hydrocarbons, of which 2,3,7,8-tetrachloro-p-dioxin (TCDD) is the prototype compound, elicit a variety of toxic, teratogenic, and carcinogenic responses in exposed animals and in humans.In cultured cells, TCDD shows marked effects on the regulation of cell cycle progression, including thymocyte apoptosis, induction of keratinocyte proliferation and terminal differentiation, and inhibition of estrogendependent proliferation in breast cancer cells. The presence of an LXCXE domain in the dioxin aromatic hydrocarbon receptor (AHR), suggested that the effects of TCDD on cell cycle regulation might be mediated by protein-protein interactions between AHR and the retinoblastoma protein (RB). Using the yeast two-hybrid system, AHR and RB were in fact shown to bind to each other. In vitro pull-down experiments with truncated AHR peptides indicated that at least two separate AHR domains form independent complexes with hypophosphorylated RB. Coimmunoprecipitation of whole cell lysates from human breast carcinoma MCF-7 cells, which express both proteins endogenously, revealed that AHR associates with RB in vivo only after receptor transformation and nuclear translocation. However, the AHR nuclear translocator and transcriptional heterodimerization partner, is not required for (nor is it a part of) the AHR⅐RB complexes detected in vitro. Ectopic expression of AHR and RB in human osteosarcoma SAOS-2 cells, which lack endogenous expression of both proteins, showed that AHR synergizes with RB to repress E2F-dependent transcription and to induce cell cycle arrest. Furthermore, AHR partly blocked T-antigen-mediated reversal of RB-dependent transcriptional repression. These results uncover a potential function for the AHR in cell cycle regulation and suggest that this function may be that of serving as an environmental sensor that signals cell cycle arrest when cells are exposed to certain environmental toxicants.

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“…[57][58][59] Exposure to dioxin leads to profound suppression of both humoral and cellular immune responses. 60 Dioxin-activated AhR suppresses T-cells, which are its primary targets, and mediates B-cell antibody response inhibition [61][62][63] and thymic involution, with consequent thymocyte loss, premature migration of T-cell progenitors, [64][65][66] and overexpression of FAS-L in thymic stromal cells, resulting in Tcell apoptosis induction. 67,68 Alterations in thymocytes appear transient, as adult mice exposed developmentally to dioxin do not exhibit thymic atrophy or alterations in the proportion of thymocyte subpopulations, and skewing of T-cell subpopulations is not observed in secondary lymphoid organs.…”

Section: Mechanisms Of Tumor Immune Escapementioning

confidence: 99%

Cancer immunoediting and dioxin-activating aryl hydrocarbon receptor: a missing link in the shift toward tumor immunoescape?

Ridolfi

Giusti

Ridolfi

2010

J Nucleic Acids Invest

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Immunological Effects of Chlorinated Dibenzo-p-Dioxins

Abstract: 2,3,7, 47-53 (1995)

Cited by 45 publications

References 62 publications

Immunologic biomarkers in relation to exposure markers of PCBs and dioxins in Flemish adolescents (Belgium).

Immunologic biomarkers in relation to exposure markers of PCBs and dioxins in Flemish adolescents (Belgium).

Aromatic Hydrocarbon Receptor Interaction with the Retinoblastoma Protein Potentiates Repression of E2F-dependent Transcription and Cell Cycle Arrest

Cancer immunoediting and dioxin-activating aryl hydrocarbon receptor: a missing link in the shift toward tumor immunoescape?

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