Chemopreventive mechanisms of methionine on inhibition of benzo(a)pyrene-DNA adducts formation in human hepatocellular carcinoma HepG2 cells

Taehyun Roh, Min Young Kwak, Eun Hwa Kwak, Dong Hyun Kim, Eun Young Han, Jung Yun Bae, Du Yeon Bang, Duck Soo Lim, Il Young Ahn, Dong Eun Jang, Seong Kwang Lim, Sun Dong Yoo, Seung Jun Kwack, Kiu Lea Park, Young Ju Lee, Kyu Bong Kim, Jaewon Lee, Hyung Sik Kim, Byung Mu Lee

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

This study was designed to investigate the molecular mechanism underlying the chemopreventive effects of methionine on benzo[a]pyrene (B[a]P)-DNA adducts formation in HepG2 cells. Methionine significantly inhibited B[a]P-DNA adduct formation in HepG2 cells. Methionine significantly decreased the cellular uptake of [ 3H] B[a]P, but increased the cellular discharge of [ 3H] B[a]P from HepG2 cells into the media. B[a]P significantly lowered total cellular glutathione (GSH) level, but co-cultured with B[a]P and methionine, gradually attenuated intracellular GSH levels in a concentration-dependent manner, which was markedly higher at 20-500μM methionine. The cellular proteins of treated cells were resolved by 2D-polyacrylamide gel electrophoresis. Proteomic profiles showed that phase II enzymes such as glutathione S-transferase (GST) omega-1, GSTM3, glyoxalase I (GLO1) and superoxide dismutase (SOD) were down-regulated by B[a]P treatment, whereas cathepsin B (CTSB), Rho GDP-dissociation inhibitor alpha (Rho-GDP-DIA), histamine N-methyltransferase (HNMT), spermidine synthase (SRM) and arginase-1 (ARG1) were up-regulated by B[a]P. B[a]P and methionine treatments, GST omega-1, GSTM3, GLO1 and SOD were significantly enhanced compared to B[a]P alone. Similarly, methionine was effective in diminishing the B[a]P-induced up-regulation of CTSB, Rho-GDP-DIA, HNMT, SRM and ARG1. Our data suggests that methionine might exert a chemoprotective effect on B[a]P-DNA adduct formation by attenuating intracellular GSH levels, blocking the uptake of B[a]P into cells, or by altering expression of proteins involved in DNA adduct formation.

Original languageEnglish (US)
Pages (from-to)232-238
Number of pages7
JournalToxicology Letters
Volume208
Issue number3
DOIs
StatePublished - Feb 5 2012

Keywords

  • Benzo[a]pyrene
  • Chemoprevention
  • DNA adduct
  • Methionine
  • Proteomics

ASJC Scopus subject areas

  • Toxicology

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