Activity of sulfotransferase 1A1 is dramatically upregulated in patients with hepatocellular carcinoma secondary to chronic hepatitis B virus infection.
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.
Wang
Xiang-Rui
XR
Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
Qu
Zeng-Qiang
ZQ
Li
Xiao-Dong
XD
Liu
Hai-Lin
HL
He
Ping
P
Fang
Bei-Xiong
BX
Xiao
Jie
J
Huang
Wei
W
Wu
Meng-Chao
MC
D000082:Acetaminophen / Q000378:metabolism; D000328:Adult; D000368:Aged; D015239:Arylsulfotransferase / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000209:etiology; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation
D000082:Acetaminophen; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human