Hexachlorobenzene-Induced Immunomodulation and Skin and Lung Lesions: A Comparison between Brown Norway, Lewis, and Wistar Rats

Michielsen, C; Bloksma, N.; Ultée, A. J.; Mil, F. van; Vos, J.G.

doi:10.1006/taap.1997.8104

Cited by 39 publications

(59 citation statements)

References 22 publications

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“…It is likely that this thymus atrophy is caused by stress, as typical stress-induced alterations (Kuper et al 2002) were observed. No significant differences in MLN weight were found, but histopathology of MLN of the high-dose group showed comparable morphology as reported previously (Michielsen et al 1997).…”

Section: Body Weight Gain Macroscopic Skin Lesions and Organ Weightssupporting

confidence: 86%

“…In HCB-exposed rats, macrophage infiltrations were observed in skin, lung (Michielsen et al 1997), spleen (Ezendam et al 2004;Schielen et al 1993), and liver (Courtney 1979). As expected, HCB increased gene expression of macrophage markers in spleen and MLN and Kupffer cell markers in liver, supporting the significance of macrophages in HCB-induced immunotoxicity.…”

Section: Inflammatory Responsesupporting

confidence: 74%

“…This finding may also be explained by a characteristic of the BN rat, a strain that tends to respond in a more T helper-2-skewed fashion. Basal levels of serum IgE are high, and HCB increases IgE levels even more (Michielsen et al 1997 (Mantovani et al 1998). …”

Section: Inflammatory Responsementioning

confidence: 99%

“…Exposure caused a dose-dependent immunostimulation characterized by enlarged spleen and LNs and increased serum levels of total IgM, IgG, IgE, and IgM against single-stranded (ss)DNA. Furthermore, rats developed inflammatory skin and lung effects characterized by infiltrates of eosinophilic granulocytes and macrophages (Michielsen et al 1997(Michielsen et al , 1999. Although both T cells and macrophages seem to play an important role in HCB-induced immunotoxicity in BN rats (Ezendam et al 2004), exact mechanisms are unknown.…”

mentioning

confidence: 99%

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Toxicogenomics of Subchronic Hexachlorobenzene Exposure in Brown Norway Rats

Ezendam¹,

Staedtler²,

Pennings³

et al. 2004

Environ. Health Perspect.

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) for performing the radioimmunoassay to determine antiacetylcholine receptor antibodies, and we thank B. Baumann (RIVM, Bilthoven, the Netherlands) for measuring the dioxin-like contamination of HCB.The authors declare they have no competing financial interests.Received 13 Hexachlorobenzene (HCB) is a persistent environmental pollutant with toxic effects in man and rat. Reported adverse effects are hepatic porphyria, neurotoxicity, and adverse effects on the reproductive and immune system. To obtain more insight into HCB-induced mechanisms of toxicity, we studied gene expression levels using DNA microarrays. For 4 weeks, Brown Norway rats were fed a diet supplemented with 0, 150, or 450 mg HCB/kg. Spleen, mesenteric lymph nodes (MLN), thymus, blood, liver, and kidney were collected and analyzed using the Affymetrix rat RGU-34A GeneChip microarray. Most significant (p < 0.001) changes, compared to the control group, occurred in spleen, followed by liver, kidney, blood, and MLN, but only a few genes were affected in thymus. This was to be expected, as the thymus is not a target organ of HCB. Transcriptome profiles confirmed known effects of HCB such as stimulatory effects on the immune system and induction of enzymes involved in drug metabolism, porphyria, and the reproductive system. In line with previous histopathological findings were increased transcript levels of markers for granulocytes and macrophages. New findings include the upregulation of genes encoding proinflammatory cytokines, antioxidants, acute phase proteins, mast cell markers, complements, chemokines, and cell adhesion molecules. Generally, gene expression data provide evidence that HCB induces a systemic inflammatory response, accompanied by oxidative stress and an acute phase response. In conclusion, this study confirms previously observed (immuno)toxicological effects of HCB but also reveals several new and mechanistically relevant gene products. Thus, transcriptome profiles can be used as markers for several of the processes that occur after HCB exposure.

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Section: Body Weight Gain Macroscopic Skin Lesions and Organ Weightssupporting

confidence: 86%

Section: Inflammatory Responsesupporting

confidence: 74%

Section: Inflammatory Responsementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Toxicogenomics of Subchronic Hexachlorobenzene Exposure in Brown Norway Rats

Ezendam¹,

Staedtler²,

Pennings³

et al. 2004

Environ. Health Perspect.

View full text Add to dashboard Cite

show abstract

“…On the other hand, rats exposed to HCB presented a marked increase in lymphoid organ weights, Tand B-cell specific mitogen blastogenesis and antibody response. In particular, in Lewis rats, this chemical has been shown to stimulate the immune system, as evidenced by an increase in the expression of serum IgM, autoantibody positivity and in the number of intraepithelial T cells [50].…”

Section: Effects Of Environmental Estrogens On the Immune Systemmentioning

confidence: 99%