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Effects of carcinogen‐induced transcription factors on the activation of hepatitis B virus expression in human hepatoblastoma HepG2 cells and its implication on hepatocellular carcinomas
Author(s) -
Banerjee Ranjit,
Caruccio Lorraine,
Jing Zhang Yu,
McKercher Scott,
Santella Regina M.
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.9197
Subject(s) - hepatoblastoma , carcinogen , carcinogenesis , hepatitis b virus , microbiology and biotechnology , transcription factor , hbsag , hepatocellular carcinoma , biology , chemistry , woodchuck hepatitis virus , cancer research , hepadnaviridae , virus , virology , medicine , biochemistry , gene
To elucidate the molecular mechanisms involved in the action of common carcinogens, which can act as important cofactors in modulating hepatitis B virus–mediated hepatocellular carcinogenesis, we have investigated the influence of aflatoxin B 1 (AFB), a potent liver carcinogen, as well as benzo[a]pyrene (BP) and 4‐aminobiphenyl (4‐ABP), carcinogens in cigarette smoke, on the induction of various transcription factors in human hepatoblastoma HepG2 cells. DNA electrophoretic mobility shift assays were performed with nuclear extracts from HepG2 cells treated with 10 μmol/L AFB, 40 μmol/L BP, or 300 μmol/L 4‐ABP for 6 and 24 hours. Eight‐ and 6‐fold increases in nuclear transcription factor κB (NF‐κB), and 5‐ and 10‐fold increases in activated protein (AP‐1) transcription factor were observed with 24 hours AFB and BP treatments, respectively, whereas 4‐ABP treatment resulted in an approximately 4‐fold induction of both NF‐κB and AP‐1. Moreover, 4‐ABP gave the strongest NF‐κB activation in 6 hours of treatment. Four‐ and 10‐fold activation of stress protein was detected by a consensus heat shock factor (HSF) sequence binding probe, with AFB and BP treatments, respectively. DNA adducts were observed by immunoassays in HepG2 cells treated with AFB and BP but not with 4‐ABP. Increased human hepatitis B virus (HBV) surface antigen (HBsAg) synthesis was detected in AFB‐ and BP‐treated HepG2 cells following transfection with recircularized HBV DNA. These data suggest that certain carcinogen‐induced transcription factors may influence viral carcinogenesis and initiate hepatocellular carcinomas (HCC).