Effects of menthol on tobacco smoke exposure nicotine dependence and NNAL glucuronidation

摘要

Menthol is a controversial cigarette additive because its’ physiological or pharmacologic effects may possibly increase the risk of cancer and its targeted market is the black community. In a community-based cross-sectional study of 525 black and white volunteers, we compared levels of urinary and plasma cotinine, plasma thiocyanate, urinary 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAL) and its detoxified form NNAL-Gluc between menthol and nonmenthol smokers. In regression models that adjusted for daily cigarette intake, no significant differences were observed in the concentration of these biomarkers by menthol status in both races. There was no significant association between high Fagerstrom nicotine dependence scores and the use of menthol cigarettes (odds ratio [OR] = 1.1, 95% confidence intervals [CI] 0.6–2.0), but an increased risk was observed with smoking a cigarette soon (≤30 minutes) after waking (OR = 2.1, 95% CI 1.0–3.8). The ratio of NNAL-Gluc to NNAL, a possible indicator of lung cancer risk, was significantly lower in menthol vs. nonmenthol smokers. The NNAL-Gluc/NNAL ratio was 34% lower in whites (P<0.01) and 22% lower in blacks. In subsequent human liver microsome studies, menthol inhibited the rate of both NNAL-O-glucuronidation and NNAL-N-glucuronidation. Collectively, these results show that menthol does not affect biological exposure to tobacco smoke constituents, but indicates that menthol might inhibit the detoxification of the potent lung carcinogen NNAL.