Mrozikiewicz Przemysław M, Grześkowiak Edmund, Seremak-Mrozikiewicz Agnieszka, Bogacz Anna, Barlik Magdalena, Semczuk Andrzej, Bartkowiak-Wieczorek Joann, Drews Krzysztof
Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznan, Poland.
Ginekol Pol. 2011 Dec;82(12):925-32.
Human cytochrome P450 1A 1 is one of the most important enzymes participating in human carcinogenesis because it metabolites several procarcinogens to active carcinogenic metabolites. Additionally enzymes of CYP450 family play an important role in estrogenes catabolization (17-beta-estradiol and estron) to intermediate products (2-, 4-hydroxyestradiol and 2-, 4-hydroxyestrone) including CYP1A1 that catalyses hydroxylation to 2-hydroxyestrogens in the endometrium. Derivates of these compounds (4-hydroxyestrogens) are carcinogenic and could induce DNA damage leading to tumour transformation. The presence of CYP1A1 enzyme in genital tract tissues could induce chemical carcinogenesis initiating cancer development. Recent studies also confirmed the role of CYP1A1 in the development of ovarian and endometrial cancer in humans. The presence of mutated CYP1A1 polymorphic variants influencing the CYP1A 1 activity could be responsible for different interindividual susceptibility to genital cancers in women.
人细胞色素P450 1A1是参与人类致癌过程的最重要酶之一，因为它能将多种前致癌物代谢为活性致癌代谢物。此外，细胞色素P450家族的酶在雌激素（17-β-雌二醇和雌酮）分解为中间产物（2-、4-羟基雌二醇和2-、4-羟基雌酮）的过程中起重要作用，其中包括在子宫内膜中将雌激素催化羟基化为2-羟基雌激素的CYP1A1。这些化合物（4-羟基雌激素）的衍生物具有致癌性，可导致DNA损伤，进而引发肿瘤转化。生殖道组织中CYP1A1酶的存在可诱发化学致癌作用，启动癌症发展。最近的研究也证实了CYP1A1在人类卵巢癌和子宫内膜癌发展中的作用。影响CYP1A1活性的突变型CYP1A1多态变体的存在可能是女性对生殖系统癌症个体易感性差异的原因。
