Racial differences in exposure and glucuronidation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). 2005

Joshua E Muscat, and Mirjana V Djordjevic, and Stephen Colosimo, and Steven D Stellman, and John P Richie
Department of Health Evaluation Sciences, Pennsylvania State Cancer Institute, Pennsylvania State College of Medicine, Hershey, PA 17033, USA. jmuscat@hmc.psu.edu

BACKGROUND In the United States, Blacks who smoke cigarettes have a higher mean blood concentration of the nicotine metabolite cotinine than White smokers. It has not been determined whether there are racial differences in the exposure to the cigarette smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and in the detoxification of NNK metabolites. METHODS A community-based cross-sectional survey of 69 Black and 93 White smokers was conducted in lower Westchester County, New York. Information on smoking and lifestyle habits was collected and urinary concentrations of several tobacco smoke biomarkers were compared, including the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). A frequency histogram and probit plot of NNAL-Gluc:NNAL ratios were constructed to determine slow and rapid glucuronidation phenotypes. RESULTS The mean concentrations of total NNAL, urinary cotinine, plasma cotinine, and thiocyanate were significantly higher in Black men than in White men for each cigarette smoked. In women, the only biomarker that was significantly elevated in Blacks was plasma cotinine. A higher proportion of White versus Black women was categorized as "rapid" glucuronidators (two-tailed exact test, P = 0.03). In men, there were no significant differences in NNAL-Gluc:NNAL phenotypes. CONCLUSIONS The higher rates of lung carcinoma in black men may be due in part to a higher level of exposure to tobacco smoke carcinogens.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009602 Nitrosamines A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. Nitrosamine
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D003367 Cotinine The N-glucuronide conjugate of cotinine is a major urinary metabolite of NICOTINE. It thus serves as a biomarker of exposure to tobacco SMOKING. It has CNS stimulating properties. Scotine
D005260 Female Females
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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