Dioxin Emissions from a Solid Waste Incinerator and Risk of Non-Hodgkin Lymphoma

Floret, N.; Mauny, Frédéric; Challier, Bruno; Arveux, Patrick; Cahn, Jean‐Yves; Viel, Jean‐François

doi:10.1097/01.ede.0000072107.90304.01

Cited by 86 publications

(51 citation statements)

References 19 publications

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“…It is presently unclear whether exposure to TCDD can lead to sustained Pax5 elevation in B cells and their precursors (Gaidano et al, 2003). Nevertheless, the findings by Krenacs et al (1998) are intriguing in light of several epidemiological studies reporting a positive, although in most cases a weak, association between non-Hodgkin's lymphomas and exposure to certain classes of chemicals including phenoxyacetic acids, chlorophenols, dioxins, dibenzofurans, and polychlorinated biphenyls (Rothman et al, 1997;Hardell et al, 1998;Viel et al, 2000;Floret et al, 2003;Engel et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

2,3,7,8-Tetrachlorodibenzo-p-dioxin-Mediated Impairment of B Cell Differentiation Involves Dysregulation of Paired Box 5 (Pax5) Isoform, Pax5a

Schneider¹,

Manzan²,

Crawford³

et al. 2008

J Pharmacol Exp Ther

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The persistent environmental contaminant and immunotoxicant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), markedly suppresses humoral immune responses. We recently reported impaired down-regulation of paired box 5 (Pax5), a repressor of B cell differentiation and concomitant suppression of the IgM response by TCDD in the murine CH12.LX B cell line. The objectives of the current study were to determine the impact of TCDD treatment on molecular outcomes characteristic of terminal B cell differentiation and to assess the role that Pax5 isoforms plays in the suppression of B cell differentiation by TCDD. In this study, we show that the highly abundant fulllength Pax5 isoform, Pax5a, and at least two additional modestly expressed Pax5 isoforms were expressed in CH12.LX and splenic B cells. In lipopolysaccharide (LPS)-activated B cells, all of the identified Pax5 isoforms were synchronously down-regulated, and in the presence of TCDD cotreatment they were abnormally and synchronously elevated, suggesting a common mechanism of regulation. Furthermore, B cell differentiation markers X-box protein-1 and major histocompatibility complex class II showed that the levels to which Pax5 was derepressed by TCDD were sufficient to impair B cell differentiation and immunoglobulin gene expression. Confirming the involvement of Pax5, ectopic expression of Pax5a in the LPS-activated CH12.LX cells closely mimicked the suppression of the IgM response by TCDD. In summary, our results demonstrate that Pax5a has a critical role in both the TCDD-mediated impairment of B cell differentiation and the suppression of the humoral immune response.Suppression of primary humoral immune responses is one of the most sensitive sequela associated with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a ubiquitous environmental contaminant. This suppression is characterized by a striking reduction in plasma cell formation and IgM secretion, and it is mediated through a direct effect by TCDD on B cells (Holsapple et al., 1986;Sulentic et al., 1998). TCDD serves as a ligand for the basic-helix-loop-helix/periodicity/ aryl hydrocarbon receptor (AHR) nuclear translocator (ARNT)/simple-minded family protein, AHR (Hankinson, 1995). Previous studies in mice and B cell lines that differ in AHR expression demonstrated the involvement of AHR in the suppression of humoral immune responses (Vecchi et al., 1983;Kerkvliet et al., 1990;Sulentic et al., 1998;Sulentic et al., 2000). The AHR is a 95 to 110-kDa cytoplasmic receptor (Burbach et al., 1992) that exists as part of a multimeric complex composed of dimers of heat shock protein 90 and the AHR-interactive protein (Bell and Poland, 2000;Petrulis and Perdew, 2002). Binding of TCDD to the AHR results in both the dissociation of AHR from the cytosolic complex and the nuclear translocation of the receptor where it releases heat shock protein 90 subunits and undergoes dimerization with ARNT (Whitelaw et al., 1995;Rowlands and Gustafsson, 1997). The interaction of the AHR/ARNT dimers with dioxinresponse e...

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Section: Discussionmentioning

confidence: 99%

2,3,7,8-Tetrachlorodibenzo-p-dioxin-Mediated Impairment of B Cell Differentiation Involves Dysregulation of Paired Box 5 (Pax5) Isoform, Pax5a

Schneider¹,

Manzan²,

Crawford³

et al. 2008

J Pharmacol Exp Ther

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“…A subsequent population-based case-control study was conducted in the same geographical area, and an OR of 2.3 (95% CI: 1.4-3.8) was reported for individuals in the high dioxin exposure category. 163 Lampi et al 135 reported a significantly positive association with NHL risk in a Finnish community whose water system was contaminated with chlorophenols (RR 5 2.8, 95% CI: 1.4-5.6). Individual exposure measurements were not available in these studies.…”

Section: Occupational and Environmental Factors Occupational And Envimentioning

confidence: 99%

The non-Hodgkin lymphomas: A review of the epidemiologic literature

et al. 2007

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“…Our team first detected a cluster of NHL in an area surrounding an MSWI with high levels of dioxin emissions (Besançon, France) (Viel et al, 2000). Subsequently, an increased risk (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.4 to 3.8) of NHL was associated with residence under the plume of this MSWI (Floret et al, 2003). These findings have recently been replicated at the national level with a similar exposure assessment approach (Viel et al, 2008).…”

Section: Introductionmentioning

confidence: 84%

Increased risk of non-Hodgkin lymphoma and serum organochlorine concentrations among neighbors of a municipal solid waste incinerator

Viel¹,

Floret²,

Deconinck³

et al. 2011

Environment International

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Organochlorine chemicals may contribute to an increased risk of non-Hodgkin lymphoma (NHL) within nonoccupationally exposed populations. Among these chemicals, dioxins and furans were mainly released by municipal solid waste incinerators (MSWIs) until a recent past in France, a source of exposure that is of public concern. We investigated organochlorines and the risk of NHL among neighbors of a French MSWI with high levels of dioxin emissions (Besançon, France), using serum concentrations to assess exposure. The study area consisted of three electoral wards, containing or surrounding the MSWI. Pesticides, dioxins, furans, and polychlorinated biphenyls (PCBs) were measured in the serum of 34 newly diagnosed NHL cases (2003)(2004)(2005) and 34 controls. Risks of NHL associated with each lipid-corrected serum concentration were estimated using exact logistic regression. The pesticides β-hexachlorocyclohexane (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.00-1.12, per 10 ng/g lipid) and p,p' dichloro-diphenyl-trichloroethane (DDT) (OR = 1.20, 95% CI = 1.01-1.45, per 10 ng/g lipid) were associated with NHL risk. Evidence indicated an increased NHL risk associated with cumulative WHO 1998 -toxic equivalency factor (TEQ) concentrations (dioxins, OR = 1.12, 95% CI = 1.03-1.26; furans, OR = 1.16, 95% CI = 1.03-1.35; dioxin-like PCBs, OR = 1.04, 95% CI = 1.00-1.07; and total TEQ, OR = 1.04, 95% CI = 1.01-1.05), as well as with non dioxin-like PCBs (OR = 1.02, 95% CI = 1.01-1.05, per 10 ng/g lipid). Most congener-specific associations were statistically significant. This study provides strong and consistent support for an association between serum cumulative WHO 1998 -TEQ concentrations, at levels experienced by people residing in the vicinity of a polluting MSWI, and risk of NHL.

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Dioxin Emissions from a Solid Waste Incinerator and Risk of Non-Hodgkin Lymphoma

Cited by 86 publications

References 19 publications

2,3,7,8-Tetrachlorodibenzo-p-dioxin-Mediated Impairment of B Cell Differentiation Involves Dysregulation of Paired Box 5 (Pax5) Isoform, Pax5a

2,3,7,8-Tetrachlorodibenzo-p-dioxin-Mediated Impairment of B Cell Differentiation Involves Dysregulation of Paired Box 5 (Pax5) Isoform, Pax5a

The non-Hodgkin lymphomas: A review of the epidemiologic literature

Increased risk of non-Hodgkin lymphoma and serum organochlorine concentrations among neighbors of a municipal solid waste incinerator

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