The feasibility of urinary biomarkers as a tool for assessing exposure to mainstream cigarette smoke carcinogen?

Abstract

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The aim of this study is to evaluate the relationship between emissions of select constituents in mainstream cigarette smoke, mentholation of cigarettes, and smokers’ gender and the levels of urinary biomarkers of exposure. For examining the effects of carcinogen emissions we compared excretion of urinary metabolites among individuals who smoked light-yield cigarettes (FTC nicotine 0.1-0.8 mg/cigarette, mean 0.66, n=87), medium-yield cigarettes (FTC nicotine 0.9-1.2 mg/cigarette, mean 1.1, n=109) and high-yield cigarettes (FTC nicotine >1.3 mg/cigarette, mean 1.41, n=61). The biomarkers monitored in this study were cotinine, a metabolite of nicotine, 4-(methylnitrosamino)-1(3-pyridyl)-1-butanol (NNAL), a metabolite of NNK, and 1-hydroxypyrene (1-OH-P), a surrogate for exposure to carcinogenic benzo(a)pyrene (BaP). In general, levels of urinary metabolites, on per cigarette basis, in these three groups did not differ significantly. However, when adjusted for the emissions of parent compounds in mainstream cigarette smoke, as determine by mimicking human smoking behavior, we found that with increasing toxins yields in mainstream smoke the conversion of carcinogens to their metabolites and excretion in urine decrease. Among smokers of light-, medium-, and high-yield cigarette the respective ratios of cotinine/nicotine (ng/mg creat./mg/day), were 90.3, 78.0, and 56.1; NNAL/NNK (pmol/mg creat./μg/day), were 0.81, 0.54, and 0.57; ratio of 1-OH-P/BaP were (ng/g creat/ng/day) 1.55, 1.12, and 0.95. Mentholated cigarettes reduced metabolism of nicotine to cotinine, and NNK to NNAL, but did not affect the excretion of a biomarkers of exposure to PAHs. The ratios of cotinine/nicotine (ng/mg creat/mg/day) were 86.0 in menthol cigarette (n=119) vs 117.1 in non-menthol cigarette smokers, (n=123), p=0.02; the NNAL/NNK (pmol/mg creat/μg/day) were 0.69 in the menthol cigarette smokers vs 1.04 in smokers of non-menthol cigarette, p=0.0007. Finally, the excretion of urinary biomarkers of exposure to cigarette toxins were modulated by gender The levels of urinary metabolites among female smokers were higher than among male smokers for the same degree of exposure; e.g., the ratio of cotinine/nicotine (ng/mg creat./mg/day) was 98.3 in women (n=120) vs 58.7 in men (n=122), p=0.0001. NNAL/NNK (pmol/mg creat./μg/day) ratios were 0.81 in women vs 0.48 in men, p=0.0001; those of 1-OH-P/BaP (ng/g creat./ng/day) were 1.43 in women vs 0.99 in men, p=0.002. Thus conversion of cigarette smoke toxins to urinary metabolites are affected by dose, type of cigarettes and gender. Supported by NCI grant CA-68384.