The Relationship Between Maternal and Fetal CYP1A1 Genotype in Smokers and Nonsmokers to Benzo(a)pyrene Hemoglobin Adducts
Polycyclic aromatic compounds(2010)
摘要
Numerous methods exist by which we can follow exposure to tobacco smoke in experimental animals as well as in human populations. The simplest method to follow tobacco exposure is by assessing either urinary or serum cotinine levels. Although this provides an accurate assessment of short-term exposure to tobacco, it fails to provide a loan term assessment of exposure over several weeks and/or months. DNA adducts also provide effective means of monitoring exposure to tobacco smoke carcinogens. However, with the use of DNA adducts one deals with repair mechanisms, which may be altered as a result of the initial exposures. The ideal biomarker for use in assessing chemical exposures over a long-term basis is the use of the red cell protein hemoglobin. Formation of electrophilic metabolites of carcinogens has been shown to react with a variety of nucleophilic sites on hemoglobin, therefore forming covalent adducts which persists for the life of the red cell (120 days) and thus can be detected in used as a biomarker of exposure. Tobacco carcinogens must first be activated by a variety of enzymes prior to becoming electrophilic intermediates. Metabolic activation of these compounds proceeds by a number of steps, including the activation via cytochrome enzymes (CYP). Following activation of the carcinogens to a reactive electrophile, the reactive compound can form covalent adducts with DNA and protein. Following activation of the carcinogens, enzymes also are responsible for the detoxification of the reactive electrophilic metabolites. These enzymes help the body handle exposure to these compounds by facilitating detoxification and illumination of those reactive carcinogenic derivatives. The present study examined the relationship between polymorphism of CYP1A1 pharmacogenetics and hemoglobin adducts to metabolites of benzo(a)pyrene in maternal and fetal blood samples.
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关键词
tobacco,carcinogen,CYP1A1 pharmacogenetics,hemoglobin adducts,benzo(a)pyrene,pregnancy,fetus
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