内源性雌二醇（E2）对生理和药理活性具有多种影响，通常用于激素替代疗法。然而，长期和过度接触E2可能增加雌激素癌症的风险。据报道，E2的CYP1酶介导的生物转化主要涉及其解毒和致癌通路之间的平衡。在三种关键的CYP1酶（CYP1A1，CYP1A2和CYP1B1）中，CYP1A1和CYP1A2主要催化产生无毒的2-羟基雌二醇（2-OH-E2），而CYP1B1专门催化产生致基因突变的4-羟基雌二醇（4-OH-E2）。4-OH-E2可以被进一步代谢成伴随着反应性氧化物（ROS）产生的亲电醌中间体，从而引发DNA损伤。由于CYP1活性的异常变化可以极大地影响E2的生物活化过程，因此外源物对CYP1酶的调节作用对于E2相关的癌症发生发展至关重要。迄今为止，已经发现数千种天然和合成化合物具有在三个CYP1成员上显示潜在抑制和/或诱导作用的能力。一般来说，这些化学物质具有相似的平面多环骨架，其结构基序和取代基对于它们的抑制/诱导效率和对CYP1酶的选择性至关重要。本综述基于化学类别全面总结了这些已知的E2代谢CYP1的抑制剂和/或诱导剂，并讨论了它们的结构活性关系，这将有助于更好地理解外源物调节的CYP1活性与雌激素癌症易感性之间的相关性。

Endogenous estradiol (E2) exerts diverse physiological and pharmacological activities, commonly used for hormone replacement therapy. However, prolonged and excessive exposure to E2 potentially increases estrogenic cancer risk. Reportedly, CYP1 enzyme-mediated biotransformation of E2 is largely concerned with its balance between detoxification and carcinogenic pathways. Among the three key CYP1 enzymes (CYP1A1, CYP1A2, and CYP1B1), CYP1A1 and CYP1A2 mainly catalyze the formation of nontoxic 2-hydroxyestradiol (2-OH-E2), while CYP1B1 specifically catalyzes the formation of genotoxic 4-hydroxyestradiol (4-OH-E2). 4-OH-E2 can be further metabolized to electrophilic quinone intermediates accompanied by the generation of reactive oxygen species (ROS), triggering DNA damage. Since abnormal alterations in CYP1 activities can greatly affect the bioactivation process of E2, regulatory effects of xenobiotics on CYP1s are essential for E2-associated cancer development. To date, thousands of natural and synthetic compounds have been found to show potential inhibition and/or induction actions on the three CYP1 members. Generally, these chemicals share similar planar polycyclic skeletons, the structural motifs and substituent groups of which are important for their inhibitory/inductive efficiency and selectivity toward CYP1 enzymes. This review comprehensively summarizes these known inhibitors and/or inductors of E2-metabolizing CYP1s based on chemical categories and discusses their structure-activity relationships, which would contribute to better understanding of the correlation between xenobiotic-regulated CYP1 activities and estrogenic cancer susceptibility.