Defense Date

2006

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Pharmacology & Toxicology

First Advisor

Dr. Kimber L. White Jr.

Abstract

Numerous findings have suggested that the increased prevalence of childhood illnesses such as cancer, infection, and allergy may be due to environmental exposures. One such cause may be maternal smoking or passive smoke exposure. Known immunotoxicants in cigarette smoke and environmental pollution include polycyclic aromatic hydrocarbons such as 1,2:5,6 Dibenzanthracene (DBA). The objective of these studies was to evaluate the immunosuppressive effects of DBA on various stages of immune system development. Adult mice were administered DBA daily in corn oil at dose levels of 158, 500, 1580, and 5000 µglkg S.C. for 28 days. Immunosuppression was not observed at levels less than 5000 µgkg in the following immune parameters: NK cell activity, anti-CD3 antibody-mediated proliferation and mixed-leukocyte response. In contrast, holistic assays such as the PFC response to the T-dependent antigen, sRBC and the delayed type hypersensitivity response were significantly suppressed at dose levels of 500 µglkg and greater. Mice exposed to DBA in utero and through lactation showed neither immunosuppressive nor sex differences among the immune parameters tested when evaluated at weaning, postnatal day (PND) 21, or when evaluated at sexual maturity (PND 42). Transference of DBA metabolites from mother to pup is suggested by HPLC analysis of milk extracted from PND 8 pups. In contrast, juvenile mice administered DBA beginning on PND 21 at dose levels from 0.25 to 2500 µgkg for 28 days demonstrated a dose-dependent suppression (43-79%) of the PFC assay, statistically significant at or above the 2.5 µglkg dose level. Neither immunosuppressive nor sex differences were observed among the various other immune parameters evaluated. Collectively, these studies indicate that the juvenile life stage in B6C3F1 mice is the most vulnerable to DBA-induced immunotoxicity with a 200-fold enhancement in immunosuppression of the PFC response as compared to adult mice. These studies provide insight into how environmental contaminants, such as DBA, may impact children's health.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

June 2008

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