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• W2103223853 abstract "The influence of specific antibodies on molecular and cellular mechanisms of activation, detoxification and biological activity of the ubiquitous carcinogen benzo[ a ]pyrene (B[ a ]P) was investigated using a monoclonal antibody. The antibody was shown to decrease cellular uptake and metabolic activation of B[ a ]P as demonstrated by higher recovery of unmetabolized B[ a ]P and decreased formation of end-point phenol metabolites in two types of target cells. Furthermore, strong antibody reactivity with 7,8-diol-B[ a ]P provided a second chance for interrupting metabolic activation by sequestration of this intermediate metabolite in the extracellular space. The biological relevance of B[ a ]P and 7,8-diol-B[ a ]P redistribution by antibody was demonstrated by reversion of B[ a ]P-induced inhibition of proliferation of human peripheral blood lymphocytes and by inhibition of CYP 1A1 induction in HepG2 cells. Remarkably, the antibody was still protective against B[ a ]P-induced immunotoxicity even after delayed addition, suggesting a more important role of metabolites in immunotoxicity than has been appreciated so far. Although B[ a ]P is activated to 7,8-diol-B[ a ]P in the same cells that are inhibited by this metabolite, the antibody completely restored lymphocyte proliferation indicating that extracellular trapping of the 7,8-diol-B[ a ]P is biologically highly effective. Thus, repartitioning of both B[ a ]P and its metabolites by the antibody may reduce their effective concentration in susceptible target organs and therefore relieve overloaded DNA repair mechanisms and inhibit carcinogen-induced P450 induction. These in vitro data also suggest that a natural or prophylactic antibody response against carcinogens may be associated with a reduced risk of cancer." @default.
• W2103223853 created "2016-06-24" @default.
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• W2103223853 date "2005-01-06" @default.
• W2103223853 modified "2023-10-17" @default.
• W2103223853 title "Modulation of the metabolism and adverse effects of benzo[a]pyrene by a specific antibody: a novel host factor in environmental carcinogenesis?" @default.
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• W2103223853 doi "https://doi.org/10.1093/carcin/bgi010" @default.
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