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The aim of this study is to compare delivered dosages of selected smoke constituents in smokers who smoked low-yield (L) cigarettes with those who smoked high-yield (H) cigarettes and their relationship with urinary metabolites. Smoking topography data indicated that low-yield cigarette smokers (FTC mean=0.7 mg nicotine/cigt.) take significantly larger puffs, but fewer puffs per cigarette than those who smoked high-yield (FTC mean=1.1 mg nicotine/cigt.) cigarettes. Overall there were no significant differences between means of total volume of smoke intake per cigarette [543.6 (L) vs 543.0 (H) mL/cig, p=0.86] or per day between these two groups. While urinary cotinine levels were 33% greater in smokers of high-yield cigarettes, mean levels of urinary metabolites of some toxins were not significantly different between low- and high-yield cigarette smokers: cotinine, 2180 (L) vs 2917 (H) ng/mg creatinine, p=0.003; 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL), 1.75 (L) vs 1.68 (H) pmol/mg creat, p=0.61; and 1-hydroxypyrene (1-OH-P), 377 (L) vs 396 (H) ng/g creatinine, p=0.97. In contrast, mean levels of actual delivered doses of toxins were significantly lower in low-yield than in high-yield cigarette smokers: nicotine were, 1.6 (L) vs 2.2 (H) mg/cigt, p=0.0001, and benzo(a)pyrene (BaP), 15.7 (L) vs 20.1 (H) ng/cigt, p=0.001; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 139.3 (L) vs 176.6 (H) ng/cigt, p=0.02. Hence, smokers of low-yield cigarettes excrete more metabolites per delivered dosage of toxins than those who smoked high-yield cigarettes. The ratios of metabolites-to parent compounds decreased with increased delivered doses of parent toxin. Smokers who inhaled 10-20 mg nicotine per day excrete about twice as much cotinine per unit of nicotine than those who inhaled 21-40 mg nicotine per day. Similarly, the mean ratio of cotinine-to nicotine in the subgroup smoking <20 cigarettes per day was 3.5-fold higher than that in those who smoked >20 cigarettes per day. There was substantial inter-individual variation in the excretion of cotinine-to-nicotine (9-fold), NNAL-to-NNK (20-fold), and 1-OH-P-to-BaP (38-fold) among those who smoked same brand of cigarettes. In conclusion, the levels of urinary biomarkers of exposure are not directly associated with the emissions of toxins in the mainstream cigarette smoke and are highly dependent on an individual’s intensity of exposure and metabolic capacity. Hence, choosing low-yield cigarettes is not necessary less harmful alternative. Supported by NCI grant CA-68384 and CA70972.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA