Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 240, Issue 1, Pages 37-45Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2009.06.019
Keywords
Benzo[a]pyrene; Balb/c; Immunotoxicity; Cyp1a1; Cyp1b1; B cells; T cells
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Funding
- Fond National de la Recherche Luxembourg [FNR: 01/04/11]
- BFR fellowship [BFR06-081]
- Ministry of Health of Luxembourg and a AFR fellowship [TR-PHD BFR06-081]
- Fond National de la Recherche
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Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also toxic for mammalian immune cells. To develop a prophylactic immune strategy against detrimental effects of B[a]R we have immunized mice with a B[a]P-diphtheria toxoid conjugate vaccine. We showed that high levels of antibodies against B[a]P and its metabolites modulate the redistribution of these PAHs in the blood. After immunization, increased levels of B[a]P and its metabolites were recovered in the blood. B[a]P significantly suppressed the proliferative response of both T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice also the immunotoxic effect of B[a]P on IFN-gamma, IL-12, TNF-alpha production and the reduced B cell activation was restored. Finally, our results showed that specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. Thus, we demonstrate that vaccination with a B[a]P conjugate vaccine based on a carrier protein used in licensed human vaccines reduces immunotoxicity and possibly other detrimental effects associated with B[a]P. (C) 2009 Elsevier Inc. All rights reserved.
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