Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
Cancer Sci. 2010 Feb;101(2):412-5. doi: 10.1111/j.1349-7006.2009.01404.x. Epub 2009 Oct 16.
The phase I metabolizing enzyme and phase II metabolizing enzyme play vital roles in carcinogenesis, but little is known about the changes of their activities in patients with hepatocellular carcinoma (HCC) secondary to chronic hepatitis B virus (HBV) infection. In this study phenacetin, a probe drug (1 g for men and 0.85 g for women orally), was applied for the detection of sulfotransferase 1A1 (SULT1A1) and cytochrome P4501A2 (CYP1A2) activities in 82 healthy participants and 148 HCC, 106 cirrhosis, and 41 chronic hepatitis B patients. In addition, a prospective cohort study for susceptibility to HCC was performed in 205 patients with cirrhosis secondary to chronic HBV infection. Compared with the healthy participants, SLUT1A1 activity increased by 9.7-fold in the HCC patients (P < 0.01). CYP1A2 activity did not significantly differ between the healthy participants and HCC patients. CYP1A2 activity decreased by 91.2% (P < 0.01) and 67.7% (P < 0.05) in the patients with cirrhosis and chronic hepatitis B, respectively; SULT1A1 activity did not increase significantly. During an approximate 2-year follow up, three of the 46 cirrhosis patients with elevated SULT1A1 activity and normal CYP1A2 activity developed HCC, but none of the 159 cirrhosis patients used as parallel controls did (P = 0.012). These results indicate that SLUT1A1 activity is dramatically upregulated in patients with HCC secondary to chronic HBV infection. The upregulation of SULT1A1 activity is not caused by the tumor itself. The interaction between SULT1A1 and CYP1A2 can play an important role in hepatocarcinogenesis in the Chinese population.
I 期代谢酶和 II 期代谢酶在致癌作用中起着至关重要的作用，但对于慢性乙型肝炎病毒（HBV）感染继发的肝细胞癌（HCC）患者这些酶活性的变化知之甚少。在这项研究中，应用了苯佐卡因（一种探针药物，男性 1 克，女性 0.85 克口服）来检测 82 名健康参与者和 148 例 HCC、106 例肝硬化和 41 例慢性乙型肝炎患者的磺基转移酶 1A1（SULT1A1）和细胞色素 P4501A2（CYP1A2）活性。此外，对 205 例由慢性 HBV 感染引起的肝硬化患者进行了 HCC 易感性的前瞻性队列研究。与健康参与者相比，HCC 患者的 SULT1A1 活性增加了 9.7 倍（P < 0.01）。健康参与者和 HCC 患者之间的 CYP1A2 活性无显著差异。肝硬化和慢性乙型肝炎患者的 CYP1A2 活性分别下降了 91.2%（P < 0.01）和 67.7%（P < 0.05）；SULT1A1 活性无明显增加。在大约 2 年的随访期间，46 例 SULT1A1 活性升高且 CYP1A2 活性正常的肝硬化患者中有 3 例发生 HCC，但作为平行对照的 159 例肝硬化患者无一例发生（P = 0.012）。这些结果表明，在慢性 HBV 感染继发的 HCC 患者中，SULT1A1 活性显著上调。SULT1A1 活性的上调不是由肿瘤本身引起的。SULT1A1 和 CYP1A2 之间的相互作用可能在中国人群中在肝癌发生中发挥重要作用。
