title: Methionine restriction inhibits chemically-induced malignant transformation in the BALB/c 3T3 cell transformation assay.
abstract: High consumption of red meat entails a higher risk of developing colorectal cancer. Methionine, which is more frequently a component of animal proteins, and folic acid are members of the one carbon cycle and as such important players in DNA methylation and cancer development. Therefore, dietary modifications involving altered methionine and folic acid content might inhibit colon cancer development. In the present study, the BALB/c 3T3 cell transformation assay was used to investigate whether methionine and folic acid are able to influence the malignant transformation of mouse fibroblasts after treatment with the known tumour initiator 3-methylcholanthrene. Three different methionine concentrations (representing a -40%, a "normal" and a +40% cell culture medium concentration, respectively) and two different folic acid concentrations (6 and 20 μM) were thereby investigated. Methionine restriction led to a decrease of type III foci, while enhancement of both methionine and folic acid did not significantly increase the cell transformation rate. Interestingly, the focus-lowering effect of methionine was only significant in conjunction with an elevated folic acid concentration. In summary, we conclude that the malignant transformation of mouse fibroblasts is influenced by methionine levels and that methionine restriction could be a possible approach to reduce cancer development.
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Nicken
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany. Electronic address: michael.empl@tiho-hannover.de.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Empl
authors.affiliation: School of Mathematics and Statistics, University of Canterbury, Private Bag 4800, 8140 Christchurch, New Zealand.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gerhard
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hausmann
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany.
authors.forename: Pablo
authors.initials: P
authors.lastname: Steinberg
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005492:Folic Acid / Q000494:pharmacology*; D008715:Methionine / Q000172:deficiency*; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D014803:Vitamin B Complex; D008748:Methylcholanthrene; D005492:Folic Acid; D008715:Methionine
keywords: BALB/c 3T3 cell transformation assay; Carcinogenesis; Diet intervention; Folic acid; Methionine; Methylation; One carbon cycle