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Immunosupression of T-dependent antibody responses by polycyclic aromatic hydrocarbons and arsenic in spleen cells from C57BL/6J mice


Please use this identifier to cite or link to this item: http://hdl.handle.net/1928/11171

Immunosupression of T-dependent antibody responses by polycyclic aromatic hydrocarbons and arsenic in spleen cells from C57BL/6J mice

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dc.contributor.author Li, Qian
dc.date.accessioned 2010-09-10T19:30:39Z
dc.date.available 2010-09-10T19:30:39Z
dc.date.issued 2010-09-10
dc.date.submitted July 2010
dc.identifier.uri http://hdl.handle.net/1928/11171
dc.description.abstract Polycyclic aromatic hydrocarbons (PAHs) and arsenic are both toxic contaminants that are widely distributed in the environment. Previous studies have shown that certain levels of PAHs and arsenic exposure individually can lead to immune suppression and carcinogenesis. Co-exposures to these two classes of chemicals are commonly seen in the environment. However, no previous studies have evaluated the immunotoxicity following simultaneous exposure to both arsenic and PAHs. Therefore, the purpose of this study was to define the immunotoxicity of selected PAHs and arsenic in a murine spleen cell system, and to elucidate possible toxicological mechanisms. Spleen cells were isolated from male C57BL/6J wild-type mice and treated with PAHs and/or arsenic. The immunotoxicological assay used in this study was the T-dependent antibody response (TDAR) to sheep red blood cells (SRBC), measured by a direct plaque forming cell (PFC) assay. Cell viability was examined using trypan blue staining. Spleen cell viability was not altered following four days of PAHs and/or arsenic in vitro treatment compared to vehicle control. However, the TDAR demonstrated that the IgM antibody response was suppressed by both PAHs and arsenic in a dose-dependent manner. The PAHs and certain metabolites, including benzo[a]pyrene (BaP), BaP-7,8- diol, benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), 7,12-dimethylbenz[a]anthracene (DMBA), DMBA-3,4-diol, dibenzo[a,l]pyrene (DB[a,l]P). PAH metabolites were found to be more potent than parent compounds in producing immunosuppression. Interestingly, DB[a,l]P, a recently discovered potent carcinogenic PAH, was found to be strongly immunosuppressive following in vitro exposures. Sodium arsenite (As+3) was found to be more potent than sodium arsenate (As+5) in suppressing the TDAR. In addition, combination treatments of PAHs and arsenic at low doses exhibited significantly greater immunosuppressive effects than PAHs by themselves, suggesting that arsenic potentiates PAH immunosuppression. Further evidence from Western blots revealed that PAHs and As+3 both triggered a p53 protein up-regulation or stabilization. Combined low dose exposure of PAHs and As+3 demonstrated an additive p53 response that was stronger than individual treatment with PAHs or As+3. Taken together, these studies demonstrated that PAHs and arsenic suppress the TDAR in spleen cells from C57BL/6J wild-type mice, and low-dose combinations of these chemicals produced synergistic immunosuppression in vitro. We also demonstrated a potential role for p53 in both PAHs and arsenic induced immunotoxicity. en_US
dc.description.sponsorship UNM Environmental Health Signature Program, UNM College of Pharmacy en_US
dc.language.iso en_US en_US
dc.subject Immunotoxicity en_US
dc.subject PAHs en_US
dc.subject Arsenic en_US
dc.subject TDAR en_US
dc.subject.lcsh Polycyclic aromatic hydrocarbons--Toxicology.
dc.subject.lcsh Arsenic--Toxicology.
dc.subject.lcsh Immunosuppression.
dc.subject.lcsh Cocarcinogenesis.
dc.subject.lcsh Chemical carcinogenesis.
dc.subject.lcsh Spleen--Pathophysiology.
dc.title Immunosupression of T-dependent antibody responses by polycyclic aromatic hydrocarbons and arsenic in spleen cells from C57BL/6J mice en_US
dc.type Thesis en_US
dc.description.degree Biomedical Sciences en_US
dc.description.level Masters en_US
dc.description.department University of New Mexico. Biomedical Sciences Graduate Program en_US
dc.description.advisor Burchiel, Scott W.
dc.description.committee-member Laurie, Hudson
dc.description.committee-member Ke Jian, Liu

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