Wittayalertpanya Supeecha, Hinsui Yaowarat, Lawanprasert Somsong
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
J Med Assoc Thai. 2003 Jun;86 Suppl 2:S310-7.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment and originate from incomplete combustion process of organic materials. These compounds are bioactivated to reactive metabolites which bind covalently to DNA and subsequently initiate carcinogenesis. PAHs have been well established as an enzyme inducer of cytochrome P450 (CYP) such as CYP1A1 and CYP1A2. Caffeine is primarily metabolized by CYP1A2 to paraxanthine, so it has been used as a specific probe for assessing CYP1A2 activity. The purpose of this study was to compare CYP1A2 activity in female subjects that were automobile exhaust exposed and non-automobile exhaust exposed using serum paraxanthine/caffeine ratio as an index. Each subject took a 180 mg single oral dose of caffeine solution. Blood samples were collected before and 5 hours after caffeine intake. Serum samples were separated by centrifugation and stored at -20 degrees C until analysis by high performance liquid chromatography (HPLC). Carbon monoxide (CO) level in blood was also detected using spectrophotometer. The results showed that serum paraxanthine/caffeine ratio in exposed subjects was significantly higher than non-exposed subjects (mean +/- SE of 0.45 +/- 0.05 and 0.33 +/- 0.03, respectively; p < 0.05). CO level in exposed subjects was also significantly higher than non-exposed subjects (mean +/- SE of 4.03 +/- 0.21 and 3.01 +/- 0.18, respectively; p < 0.05).
Paraxanthine/caffeine ratio, as an index for CYP1A2 activity, can be used to determine PAHs exposure. Automobile exhaust exposed subjects demonstrated significantly higher CYP1A2 activity than that of the non-exposed subjects. Exposed subjects have a possibly higher risk of chemical carcinogenesis.
多环芳烃（PAHs）在环境中普遍存在，源于有机材料的不完全燃烧过程。这些化合物被生物激活为活性代谢物，它们与DNA共价结合，随后引发致癌作用。PAHs已被确认为细胞色素P450（CYP）如CYP1A1和CYP1A2的酶诱导剂。咖啡因主要通过CYP1A2代谢为副黄嘌呤，因此它已被用作评估CYP1A2活性的特异性探针。本研究的目的是以血清副黄嘌呤/咖啡因比值为指标，比较暴露于汽车尾气和未暴露于汽车尾气的女性受试者的CYP1A2活性。每位受试者单次口服180毫克咖啡因溶液。在摄入咖啡因前和摄入后5小时采集血样。通过离心分离血清样本，并在-20℃下储存，直至通过高效液相色谱（HPLC）进行分析。还使用分光光度计检测血液中的一氧化碳（CO）水平。结果显示，暴露组受试者的血清副黄嘌呤/咖啡因比值显著高于未暴露组受试者（分别为0.45±0.05和0.33±0.03的平均值±标准误；p<0.05）。暴露组受试者的CO水平也显著高于未暴露组受试者（分别为4.03±0.21和3.01±0.18的平均值±标准误；p<0.05）。
副黄嘌呤/咖啡因比值作为CYP1A2活性指标，可用于确定PAHs暴露情况。暴露于汽车尾气的受试者表现出的CYP1A2活性显著高于未暴露的受试者。暴露者发生化学致癌的风险可能更高。
