Modulation of carcinogen bioavailability by immunisation with benzo[a]pyrene-conjugate vaccines.
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.
Grova
Nathalie
N
Institute of Immunology, LNS/CRP-Santé, Grand Duchy of Luxembourg, Luxembourg.
Prodhomme
Emmanuel J F
EJ
Schellenberger
Mario T
MT
Farinelle
Sophie
S
Muller
Claude P
CP
D000818:Animals; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors*; D001682:Biological Availability; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D003429:Cross Reactions; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018074:Vaccines, Conjugate / Q000276:immunology*
D002273:Carcinogens; D018074:Vaccines, Conjugate; D001564:Benzo(a)pyrene