Dose-dependent synergistic and antagonistic mutation responses of binary mixtures of the environmental carcinogen benzo[a]pyrene with food-derived carcinogens.

Dose-dependent synergistic and antagonistic mutation responses of binary mixtures of the environmental carcinogen benzo[a]pyrene with food-derived carcinogens. Arch Toxicol. 2018 Sep 26;: Authors: David RM, Gooderham NJ Abstract Cooking food at high temperatures produces genotoxic chemicals and there is concern about their impact on human health. DNA damage caused by individual chemicals has been investigated but few studies have examined the consequences of exposure to mixtures as found in food. The current study examined the mutagenic response to binary mixtures of benzo[a]pyrene (BaP) with glycidamide (GA), BaP with acrylamide (AC), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) with GA at human-relevant concentrations (sub-nM). The metabolically competent human MCL-5 cells were exposed to these chemicals individually or in mixtures and mutagenicity was assessed at the thymidine kinase (TK) locus. Mixture exposures gave dose-responses that differed from those for the individual chemicals; for the BaP-containing mixtures, an increased mutation frequency (MF) at low concentration combinations that were not mutagenic individually, and decreased MF at higher concentration combinations, compared to the calculated predicted additive MF of the individual chemicals. In contrast, the mixture of PhIP with GA did not increase MF above background levels. These data suggest BaP is driving the mutation response and that metabolic act...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research