Benowitz Neal L, Herrera Brenda, Jacob Peyton
Division of Clinical Pharmacology and Experimental Therapeutics, University of California, San Francisco, Box 1220, San Francisco, CA 94143-1220, USA.
J Pharmacol Exp Ther. 2004 Sep;310(3):1208-15. doi: 10.1124/jpet.104.066902. Epub 2004 Apr 14.
Smoking mentholated cigarettes has been suggested to convey a greater cancer risk compared with smoking nonmentholated cigarettes. Two of the possible mechanisms by which mentholated cigarette smoking could increase risk are by increasing systemic exposure to tobacco smoke toxins and by affecting the metabolism of nicotine or tobacco smoke carcinogens. To examine these possibilities, we performed a crossover study in 14 healthy smokers, one-half of whom were African-Americans and one-half whites. Subjects were randomly assigned to smoke mentholated or nonmentholated cigarettes for 1 week, then to cross over to the other type of cigarettes for another week. Subjects were confined to a Clinical Research Center for 3 days of each week, during which time blood levels of nicotine and carbon monoxide were measured throughout the day and an intravenous infusion of deuterium-labeled nicotine and cotinine was administered to determine the rate and pathways of nicotine metabolism. The systemic intake of nicotine and carbon monoxide was, on average, not affected by mentholation of cigarettes. Mentholated cigarette smoking did significantly inhibit the metabolism of nicotine (clearance: 1289 versus 1431 ml/min, two sided, p = 0.02). Inhibition of nicotine metabolism occurred both by slower oxidative metabolism to cotinine and by slower glucuronide conjugation. Our data do not support the hypothesis that mentholated cigarette smoking results in a greater absorption of tobacco smoke toxins. Our finding of impaired metabolism of nicotine while mentholated cigarette smoking suggests that mentholated cigarette smoking enhances systemic nicotine exposure.
与吸非薄荷醇香烟相比，吸薄荷醇香烟被认为会带来更高的癌症风险。吸薄荷醇香烟可能增加风险的两种潜在机制是增加全身对烟草烟雾毒素的暴露以及影响尼古丁或烟草烟雾致癌物的代谢。为了研究这些可能性，我们对14名健康吸烟者进行了一项交叉研究，其中一半是非洲裔美国人，一半是白人。受试者被随机分配吸薄荷醇香烟或非薄荷醇香烟1周，然后交叉吸另一种香烟1周。受试者每周有3天被限制在临床研究中心，在此期间全天测量尼古丁和一氧化碳的血液水平，并静脉输注氘标记的尼古丁和可替宁以确定尼古丁代谢的速率和途径。香烟的薄荷醇化平均而言不影响尼古丁和一氧化碳的全身摄入量。吸薄荷醇香烟确实显著抑制了尼古丁的代谢（清除率：分别为1289与1431毫升/分钟，双侧，p = 0.02）。尼古丁代谢的抑制既通过向可替宁的氧化代谢减慢，也通过葡糖醛酸结合减慢而发生。我们的数据不支持吸薄荷醇香烟会导致对烟草烟雾毒素吸收增加的假设。我们发现吸薄荷醇香烟时尼古丁代谢受损表明吸薄荷醇香烟会增加全身尼古丁暴露。
