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


  • 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 [(3)H] B[a]P, but increased the cellular discharge of [(3)H] 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 20-500M 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.

published proceedings

  • Toxicol Lett

author list (cited authors)

  • Roh, T., Kwak, M. Y., Kwak, E. H., Kim, D. H., Han, E. Y., Bae, J. Y., ... Lee, B. M.

citation count

  • 16

complete list of authors

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

publication date

  • February 2012