It has been shown that mutagenic chemicals can form naturally in foods during cooking. Examples include Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon generated by incomplete combustion of organic substances such as lipids, leading to contamination of numerous foodstuffs (Lijinski and Shubik, Science 1964, 145, 53), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine that is formed during the cooking of meat (Murray, et al. J Chromatog 1993, 616, 211), and glycidamide (GA) is the ultimate genotoxic metabolite of acrylamide (AC), which forms when foods, such as potatoes and cereals, are cooked at temperatures exceeding 100°C, in a reaction between the amino acid asparagine and reducing sugars that are naturally present in these foods (Tornqvist, Adv Exp Biol Med 2005, 561, 1). These chemicals have individually been shown to be genotoxic but the biological consequences of exposure to mixtures of these chemicals have not been systematically examined. The aim of the current study was to examine the biological response of MCL-5 cells (a metabolically competent human lymphoblastoid cell line) to mixtures of these genotoxic chemicals at concentrations that are relevant to human exposure (mM to sub-nM). Cells were exposed to the chemicals individually or in mixtures for 24h and mutagenicity was assessed through resistance to trifluorothymidine at the thymidine kinase (TK) locus and 6-thioguanine at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus. The mixture exposures gave modified dose-response curves from the individual chemicals, with increased mutation frequency (MF) at some low concentration combinations that were not mutagenic individually, and decreased MF at some combinations of higher concentrations that did produce a mutation response individually. Responses also differed between the TK and HPRT loci, with a higher MF observed for high concentration combinations at HPRT compared to TK. Ethoxyresorufin-O-deethylase (EROD) activity was measured and was found to correspond to the MF at the TK locus suggesting the involvement of CYP1A family in the mutation response. These data suggest that mixtures of genotoxic chemicals produce different mutation responses to the individual chemicals. The increase in MF at some low concentration combinations where the individual chemicals are not genotoxic is of significance when considering the carcinogenic potential of food.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5454. doi:1538-7445.AM2012-5454