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

[Guest guest]

Hepatology 2000 Aug;32(2):367-374

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.

Banerjee R, Caruccio L, Jing Zhang Y, McKercher S, Santella RM

Department of Microbiology and Immunology, New York Medical College,

Valhalla, NY.

[Record supplied by publisher]

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 mumol/L

AFB, 40 mumol/L BP, or 300 mumol/L 4-ABP for 6 and 24 hours. Eight- and

6-fold increases in nuclear transcription factor kappaB (NF-kappaB), 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-kappaB

and AP-1. Moreover, 4-ABP gave the strongest NF-kappaB 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).

PMID: 10915744

[Guest guest]

Hepatology 2000 Aug;32(2):367-374

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.

Banerjee R, Caruccio L, Jing Zhang Y, McKercher S, Santella RM

Department of Microbiology and Immunology, New York Medical College,

Valhalla, NY.

[Record supplied by publisher]

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 mumol/L

AFB, 40 mumol/L BP, or 300 mumol/L 4-ABP for 6 and 24 hours. Eight- and

6-fold increases in nuclear transcription factor kappaB (NF-kappaB), 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-kappaB

and AP-1. Moreover, 4-ABP gave the strongest NF-kappaB 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).

PMID: 10915744