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Effects of antibodies induced by a conjugate vaccine on 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone absorptive transport, metabolism, and proliferation of human lung cells
Author(s) -
De Buck Stefan S.,
Schellenberger Mario T.,
Ensch Corinne,
Muller Claude P.
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25073
Subject(s) - carcinogen , nitrosamine , chemistry , antibody , cell growth , cancer research , monoclonal antibody , cell culture , in vitro , cell , microbiology and biotechnology , immunology , biochemistry , biology , genetics
One of the most abundant and potent lung carcinogen is the nicotine‐derived tobacco‐specific nitrosamine, 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK). The monoclonal antibody P9D5 induced with a NNK‐conjugate vaccine was used to investigate the ability of NNK‐specific antibodies to modulate NNK‐induced adverse effects as well as its absorptive transport and metabolism in two lung cancer cell lines (Calu‐3 and NCI‐H82). Transport experiments in Calu‐3 cells with a 50‐fold molar excess of apical P9D5 increased the recovery of coadministered apical NNK, with a concomitant decrease in NNK transepithelial transport of more than 50% compared to controls. In contrast, basolateral P9D5 did neither influence transepithelial transport of NNK nor its disappearance from the apical compartment. Calu‐3 cells were also found to reduce NNK to NNAL and a 65‐fold molar excess of NNK‐specific antibody inhibited this metabolic conversion by 46 and 54% compared to irrelevant control antibody after 48 and 72 hr, respectively. The biological relevance of NNK redistribution by antibody was demonstrated by reversion of NNK‐induced cell proliferation in NCI‐H82 cells. Repartitioning of tobacco carcinogens by antibody may reduce their early effective peak concentrations in susceptible target organs and thus relieve overloaded local DNA repair mechanisms and diminish carcinogen‐induced cell proliferation. These in vitro data therefore suggest that a prophylactic antibody response may be associated with a reduced risk of cancer.