Modulation of carcinogen bioavailability by immunisation with benzo[a]pyrene-conjugate vaccines

Nathalie Grova; Emmanuel J.F. Prodhomme; Mario T. Schellenberger; Sophie Farinelle; Claude P. Muller

doi:10.1016/j.vaccine.2009.04.052

Modulation of carcinogen bioavailability by immunisation with benzo[a]pyrene-conjugate vaccines

Nathalie Grova, Emmanuel J.F. Prodhomme, Mario T. Schellenberger, Sophie Farinelle, Claude P. Muller^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

30 Citations (Scopus)

Abstract

Benzo[a]pyrene (B[a]P) conjugate vaccines based on ovalbumin, tetanus toxoid and diphtheria toxoid (DT) as carrier proteins were developed to investigate the effect of specific antibodies on the bioavailability of this ubiquitous carcinogen and its metabolites. After metabolic activation of this prototype carcinogen, B[a]P forms DNA adducts which initiate chemical carcinogenesis. B[a]P-DT conjugate induced the most robust immune response. The antibodies reacted not only with B[a]P but also with the proximate carcinogen 7,8-diol-B[a]P. Antibodies modulated the bioavailability of B[a]P and its metabolic activation in a dose-dependent manner by sequestration in the blood. Our results showed that this immune prophylactic strategy influences the pharmacokinetic of B[a]P and further studies to investigate their effects on chemical carcinogenesis are warranted.

Original language	English
Pages (from-to)	4142-4151
Number of pages	10
Journal	Vaccine
Volume	27
Issue number	31
DOIs	https://doi.org/10.1016/j.vaccine.2009.04.052
Publication status	Published - 24 Jun 2009

Keywords

Benzo[a]pyrene
Bioavailability
Mice
Specific antibodies

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10.1016/j.vaccine.2009.04.052

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title = "Modulation of carcinogen bioavailability by immunisation with benzo[a]pyrene-conjugate vaccines",

abstract = "Benzo[a]pyrene (B[a]P) conjugate vaccines based on ovalbumin, tetanus toxoid and diphtheria toxoid (DT) as carrier proteins were developed to investigate the effect of specific antibodies on the bioavailability of this ubiquitous carcinogen and its metabolites. After metabolic activation of this prototype carcinogen, B[a]P forms DNA adducts which initiate chemical carcinogenesis. B[a]P-DT conjugate induced the most robust immune response. The antibodies reacted not only with B[a]P but also with the proximate carcinogen 7,8-diol-B[a]P. Antibodies modulated the bioavailability of B[a]P and its metabolic activation in a dose-dependent manner by sequestration in the blood. Our results showed that this immune prophylactic strategy influences the pharmacokinetic of B[a]P and further studies to investigate their effects on chemical carcinogenesis are warranted.",

keywords = "Benzo[a]pyrene, Bioavailability, Mice, Specific antibodies",

author = "Nathalie Grova and Prodhomme, {Emmanuel J.F.} and Schellenberger, {Mario T.} and Sophie Farinelle and Muller, {Claude P.}",

note = "Funding Information: We are grateful to Gilles Laverny for his excellent technical assistance. We acknowledge the support of the Fond National de la Recherche (Tobavac project, FNR: 01/04/11), and the CRP-Sant{\'e} and the Ministry of Health of Luxembourg for the continued support. ",

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AU - Prodhomme, Emmanuel J.F.

AU - Schellenberger, Mario T.

AU - Farinelle, Sophie

AU - Muller, Claude P.

N1 - Funding Information: We are grateful to Gilles Laverny for his excellent technical assistance. We acknowledge the support of the Fond National de la Recherche (Tobavac project, FNR: 01/04/11), and the CRP-Santé and the Ministry of Health of Luxembourg for the continued support.

PY - 2009/6/24

Y1 - 2009/6/24

N2 - Benzo[a]pyrene (B[a]P) conjugate vaccines based on ovalbumin, tetanus toxoid and diphtheria toxoid (DT) as carrier proteins were developed to investigate the effect of specific antibodies on the bioavailability of this ubiquitous carcinogen and its metabolites. After metabolic activation of this prototype carcinogen, B[a]P forms DNA adducts which initiate chemical carcinogenesis. B[a]P-DT conjugate induced the most robust immune response. The antibodies reacted not only with B[a]P but also with the proximate carcinogen 7,8-diol-B[a]P. Antibodies modulated the bioavailability of B[a]P and its metabolic activation in a dose-dependent manner by sequestration in the blood. Our results showed that this immune prophylactic strategy influences the pharmacokinetic of B[a]P and further studies to investigate their effects on chemical carcinogenesis are warranted.

AB - Benzo[a]pyrene (B[a]P) conjugate vaccines based on ovalbumin, tetanus toxoid and diphtheria toxoid (DT) as carrier proteins were developed to investigate the effect of specific antibodies on the bioavailability of this ubiquitous carcinogen and its metabolites. After metabolic activation of this prototype carcinogen, B[a]P forms DNA adducts which initiate chemical carcinogenesis. B[a]P-DT conjugate induced the most robust immune response. The antibodies reacted not only with B[a]P but also with the proximate carcinogen 7,8-diol-B[a]P. Antibodies modulated the bioavailability of B[a]P and its metabolic activation in a dose-dependent manner by sequestration in the blood. Our results showed that this immune prophylactic strategy influences the pharmacokinetic of B[a]P and further studies to investigate their effects on chemical carcinogenesis are warranted.

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Modulation of carcinogen bioavailability by immunisation with benzo[a]pyrene-conjugate vaccines

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Keywords

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