Chan Nelson L S, Wang Huan, Wang Yun, Leung Hau Yi, Leung Lai K
Department of Biochemistry, The Chinese University of Hong Kong, Rm. 507C MMW Bldg., Shatin, N.T., Hong Kong.
Toxicol Appl Pharmacol. 2006 Jun 1;213(2):98-104. doi: 10.1016/j.taap.2005.10.002. Epub 2005 Nov 22.
Perillyl alcohol (POH) is a dietary monoterpene with potential applications in chemoprevention and chemotherapy. Although clinical trials are under way, POH's physiological and pharmacological properties are still unclear. In the present study, the effect of POH on polycyclic aromatic hydrocarbon (PAH)-induced genotoxicity, and the related expression were examined in MCF-7 cells. Exposure to environmental toxicant increases the risk of cancer. Many of these compounds are pro-carcinogens and are biotransformed into their ultimate genotoxic structures by xenobiotic metabolizing enzymes. CYP1A1 and 1B1 are enzymes that catalyze the biotransformation of dimethylbenz[a]anthracene (DMBA). Our data revealed that 0.5 microM of POH was effective in blocking DMBA-DNA binding. Ethoxyresorufin-O-deethylase (EROD) assay indicated that the administration of POH inhibited the DMBA-induced enzyme activity in MCF-7 cells. Enzyme kinetic analysis revealed that POH inhibited CYP1B1 but not CYP1A1 activity. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay also demonstrated that the monoterpene reduced CYP1B1 mRNA abundance induced by DMBA. The present study illustrated that POH might inhibit and downregulate CYP1B1, which could protect against PAH-induced carcinogenesis.
紫苏醇（POH）是一种膳食单萜，在化学预防和化疗方面具有潜在应用价值。尽管临床试验正在进行，但POH的生理和药理特性仍不清楚。在本研究中，检测了POH对多环芳烃（PAH）诱导的基因毒性的影响以及相关表达，实验对象为MCF-7细胞。接触环境毒物会增加患癌风险。这些化合物中有许多是前致癌物，会被异生物质代谢酶生物转化为其最终的基因毒性结构。细胞色素P450 1A1（CYP1A1）和1B1是催化二甲基苯并[a]蒽（DMBA）生物转化的酶。我们的数据显示，0.5微摩尔的POH能有效阻断DMBA与DNA的结合。乙氧异吩唑酮-O-脱乙基酶（EROD）检测表明，给予POH可抑制MCF-7细胞中DMBA诱导的酶活性。酶动力学分析表明，POH抑制CYP1B1的活性，但不抑制CYP1A1的活性。定量逆转录聚合酶链反应（RT-PCR）检测也表明，该单萜可降低DMBA诱导的CYP1B1 mRNA丰度。本研究表明，POH可能抑制并下调CYP1B1，从而预防PAH诱导的致癌作用。
