The human cytochrome P450 (CYP) 1A1 gene encodes a monooxygenase that metabolizes multiple exogenous and endogenous substrates. CYP1A1 has become infamous for its oxidative metabolism of benzo[a]pyrene and related polycyclic aromatic hydrocarbons, converting these chemicals into very potent human carcinogens. CYP1A1 expression is mainly controlled by the aryl hydrocarbon receptor (AHR), a transcription factor whose activation is induced by binding of persistent organic pollutants, including polycyclic aromatic hydrocarbons and dioxins. Accordingly, induction of CYP1A1 expression and activity serves as a biomarker of AHR activation and associated xenobiotic metabolism as well as toxicity in diverse animal species and humans. Determination of CYP1A1 activity is integrated into modern toxicological concepts and testing guidelines, emphasizing the tremendous importance of this enzyme for risk assessment and regulation of chemicals. Further, CYP1A1 serves as a molecular target for chemoprevention of chemical carcinogenesis, although present literature is controversial on whether its inhibition or induction exerts beneficial effects. Regarding therapeutic applications, first anti-cancer prodrugs are available, which require a metabolic activation by CYP1A1, and thus enable a specific elimination of CYP1A1-positive tumors. However, the application range of these drugs may be limited due to the frequently observed downregulation of CYP1A1 in various human cancers, probably leading to a reduced metabolism of endogenous AHR ligands and a sustained activation of AHR and associated tumor-promoting responses. We here summarize the current knowledge on CYP1A1 as a key player in the metabolism of exogenous and endogenous substrates and as a promising target molecule for prevention and treatment of human malignancies.

人类细胞色素P450（CYP）1A1基因编码一种单加氧酶，该酶可代谢多种外源性和内源性底物。CYP1A1因其苯并[ a]的氧化代谢而臭名昭著。py和相关的多环芳烃，将这些化学物质转化为强效的人类致癌物。CYP1A1的表达主要受芳烃受体（AHR）的控制，芳烃受体是一种转录因子，其活化是由持久性有机污染物（包括多环芳烃和二恶英）的结合诱导的。因此，CYP1A1表达和活性的诱导可作为AHR活化和相关异生代谢以及不同动物物种和人类毒性的生物标志物。CYP1A1活性的测定已整合到现代毒理学概念和测试指南中，强调了该酶在风险评估和化学品调控中的巨大重要性。此外，CYP1A1用作化学预防化学致癌作用的分子靶标，尽管目前的文献在其抑制或诱导是否发挥有益作用方面存在争议。关于治疗应用，可使用第一种抗癌前药，其需要通过CYP1A1进行代谢激活，从而能够特异性消除CYP1A1阳性肿瘤。但是，由于在各种人类癌症中经常观察到CYP1A1的下调，这些药物的应用范围可能受到限制，可能导致内源性AHR配体的代谢减少以及AHR的持续活化和相关的促肿瘤反应。我们在此总结关于CYP1A1的最新知识，CYP1A1是外源性和内源性底物代谢的关键参与者，也是预防和治疗人类恶性肿瘤的有希望的靶分子。