DIFFERENCES IN THE URINARY METABOLITES OF THE TOBACCO-SPECIFIC LUNG CARCINOGEN 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN BLACK-AND-WHITE SMOKERS

Incidence and mortality rates for lung cancer in the United States are significantly greater in blacks than in whites, This disparity cannot be explained by differences in smoking behavior, We hypothesize that the observed racial differences in risk may be due to differences in t he metabolic activation or detoxification of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), To t est this, different biomarkers of NNK exposure and metabolism, includi ng the urinary metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butano l (NNAL) and the presumed detoxification product o)-1-(3-pyridyl)-but- 1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc), were examined along wi th questionnaire data on lifestyle habits and diet in a metabolic epid emiological study of 34 black and 27 white healthy smokers, Results de monstrated that urinary NNAL-Gluc:NNAL ratios, a likely indicator of N NAL glucuronidation and detoxification, were significantly greater in whites than in blacks (P < 0.02), In addition, two phenotypes were app arent by probit analysis representing poor (ratio <6) and extensive (r atio greater than or equal to 6) glucuronidation groups, The proportio n of blacks falling into the former, potentially high-risk group was s ignificantly greater than that of whites (P < 0.05), The absolute leve ls of urinary NNAL, NNAL-Gluc, and cotinine were also greater in black s than in whites when adjusted for the number of cigarettes smoked, No ne of the observed racial differences could be explained by dissimilar ities in exposure or other sociodemographic or dietary factors, Also, it is unlikely that the dissimilarities are due to racial differences in preference for mentholated cigarettes, because chronic administrati on of menthol to NNK-treated rats did not result in either increases i n urinary total NNAL or decreases in NNAL-Gluc:NNAL ratios, Altogether , these results suggest that racial differences in NNAL glucuronidatio n, a putative detoxification pathway for NNK, may explain in part the observed differences in cancer risk.