Methionine inhibits benzo(a)pyrene-DNA adducts formation in human hepatocellular carcinoma HepG2 cells

• KYUNG MinJi

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• KIM Young Woo

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• ROH Tae Hyun

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• KIM Min Ji

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• NAM Yoon A

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• CHUNG Bu Young

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• BANG Du Yeon

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• LIM Seong Kwang

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• KWON Mi Jung

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• CHO Myung Chan

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

• KWACK Seung Jun

  College of Natural Sciences, Changwon Nat’l University, Korea

• KIM Hyung Sik

  College of Natural Sciences, Changwon Nat’l University, Korea

• LEE Byung-Mu

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Korea

抄録

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 20–500 uM 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.

収録刊行物

• 日本毒性学会学術年会

  日本毒性学会学術年会 39.2 (0), AP-126-, 2012

  日本毒性学会

詳細情報

• CRID: 1390001205547159680
• NII論文ID: 130005009062
• DOI: 10.14869/toxpt.39.2.0.ap-126.0
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可