RRC ID 43925
Author Hanioka N, Nonaka Y, Saito K, Negishi T, Okamoto K, Kataoka H, Narimatsu S.
Title Effect of aflatoxin B1 on UDP-glucuronosyltransferase mRNA expression in HepG2 cells.
Journal Chemosphere
Abstract Aflatoxin B1 (AFB1) is a potent mycotoxin that induces hepatocellular carcinoma in many animal species, including humans. In this study, we examined the effects of AFB1 on UDP-glucuronosyltransferase (UGT) mRNA expression in HepG2 cells (human hepatocellular carcinoma cell line). The cells were treated with AFB1 for 48 h at a concentration of 10 μM, and their viability (87%) was not significantly different from that of control cells. Reverse transcription polymerase chain reaction (RT-PCR) analysis demonstrated that the mRNAs of four UGT1As (UGT1A1, UGT1A3, UGT1A4 and UGT1A9) and seven UGT2Bs (UGT2B4, UGT2B7, UGT2B10, UGT2B11, UGT2B15, UGT2B17 and UGT2B28) are expressed in HepG2 cells. The mRNAs of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), retinoid X receptor (RXR) and glucocorticoid receptor (GR) as transcriptional regulators were also detected. AFB1 significantly increased mRNA levels of UGT1A3, UGT2B10, UGT2B15 and UGT2B17 in HepG2 cells to 2.5-, 2.0-, 1.9- and 1.5-fold, respectively, whereas the mRNA levels of transcriptional regulators were hardly affected by AFB1. These findings suggest that AFB1 induces UGT2B isoforms rather than UGT1A isoforms in HepG2 cells, and that the change may closely contribute to the toxicity of AFB1.
Volume 89(5)
Pages 526-9
Published 2012-10-1
DOI 10.1016/j.chemosphere.2012.05.039
PII S0045-6535(12)00660-1
PMID 22749127
MeSH Aflatoxin B1 / toxicity* Gene Expression Regulation, Enzymologic / drug effects* Glucuronosyltransferase / genetics* Hep G2 Cells Humans RNA, Messenger / genetics RNA, Messenger / metabolism
IF 5.778
Times Cited 15
WOS Category ENVIRONMENTAL SCIENCES
Resource
Human and Animal Cells