Systemic immunosuppression following a single pharyngeal aspiration of 1,2:5,6-dibenzanthracene in female B₆C₃F₁ mice

Abstract

1,2:5,6-Dibenzanthracene (DBA) is ubiquitous in our environment as a contaminant produced by incomplete combustion of organics from sources such as forest fires, cigarette smoke, and asphalt paving, and it is more immunosuppressive of the T-dependent antibody-forming cell (AFC) response than the well-studied polycyclic aromatic hydrocarbon, benzo(a)pyrene. The systemic immunosuppressive effects of DBA were investigated following a single pharyngeal aspiration (pa) in female B₆C₃F₁ mice. The immunotoxic effects of DBA were evaluated using numerous assays of varying complexity to evaluate innate (natural killer [NK] cell activity), cell-mediated (T-lymphocyte proliferation, mixed leukocyte response [MLR], cytotoxic T-lymphocyte [CTL] activity, delayed-type hypersensitivity [DTH]), and humoral immunity (B-lymphocyte proliferation, T-dependent antibody responses). A single pa of DBA at doses up to 30 mg/kg had no effect on NK cell activity, anti-CD3 antibody-mediated T-lymphocyte proliferation, the MLR, or B-lymphocyte proliferation. DBA at 30 mg/kg suppressed Concanavalin A (ConA)-stimulated T-lymphocyte proliferation and the CTL response. DBA exposure reduced cytokine production in spleen cell culture supernatants after in vitro stimulation with ConA or lipopolysaccharide (LPS). Immunosuppression was observed at lower doses in the holistic assays. The DTH response to Candida albicans was significantly decreased at 3.0 mg/ kg DBA, while the AFC response was intermittently suppressed at 1.0 mg/kg, with no effect observed at 0.3 mg/kg. These results demonstrate that a single pa of DBA produces systemic immunotoxicity, and of the assays utilized, the holistic assays (i.e., DTH, AFC) appear to be most sensitive to the immunosuppressive effects of DBA.

Keywords::

• 1;2:5;6-Dibenzanthracene
• polycyclic aromatic hydrocarbon
• PAH
• immunotoxicity
• pharyngeal aspiration

Acknowledgements

Special thanks to Dr. Denise Roesh, Ronnetta Brown, Deborah Musgrove, Colleen McLoughlin, Dr. Wimolnut Auttachoat, and especially Dr. Chris Sheth. Thanks also to Dr. Jane Lewis and Dr. Debbie Koller of Altria Client Services for providing the opportunity for this project to be completed.

Declaration of interests

Dr. Kimber L. White, Jr. is the owner of a company, ImmunoTox^®, Inc., that conducts immunotoxicological studies under Good Laboratory Practices (GLP); however, none of the work presented here involved his company. Dr. Donna C. Smith is currently an employee of Altria Client Services, and the studies conducted herein were completed as a part of her doctoral thesis in the Department of Pharmacology and Toxicology at Virginia Commonwealth University. This work was supported in part by the National Institute of Environmental Health Sciences (ES 05454).