Chemopreventive mechanisms of methionine on inhibition of benzo(a)pyrene-DNA adducts formation in human hepatocellular carcinoma HepG2 cells
- Authors
- Roh, T[Roh, Taehyun]; Kwak, MY[Kwak, Min Young]; Kwak, EH[Kwak, Eun Hwa]; Kim, DH[Kim, Dong Hyun]; Han, EY[Han, Eun Young]; Bae, JY[Bae, Jung Yun]; Bang, DY[Bang, Du Yeon]; Lim, DS[Lim, Duck Soo]; Ahn, IY[Ahn, Il Young]; Jang, DE[Jang, Dong Eun]; Lim, SK[Lim, Seong Kwang]; Yoo, SD[Yoo, Sun Dong]; Kwack, SJ[Kwack, Seung Jun]; Park, KL[Park, Kiu Lea]; Lee, YJ[Lee, Young Ju]; Kim, KB[Kim, Kyu-Bong]; Lee, J[Lee, Jaewon]; Kim, HS[Kim, Hyung Sik]; Lee, BM[Lee, Byung Mu]
- Issue Date
- 5-Feb-2012
- Publisher
- ELSEVIER IRELAND LTD
- Citation
- TOXICOLOGY LETTERS, v.208, no.3, pp.232 - 238
- Indexed
- SCIE
SCOPUS
- Journal Title
- TOXICOLOGY LETTERS
- Volume
- 208
- Number
- 3
- Start Page
- 232
- End Page
- 238
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/66378
- DOI
- 10.1016/j.toxlet.2011.11.013
- ISSN
- 0378-4274
- 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 [H-3] B[a]P, but increased the cellular discharge of [3H] B[a]P from HepG2 cells into the media. B[a]13 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 mu M 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. (C) 2011 Published by Elsevier Ireland Ltd.
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