Genotoxicity of three food processing contaminants in transgenic mice expressing human sulfotransferases 1A1 and 1A2 as assessed by the in vivo alkaline single cell gel electrophoresis assay

Abstract

The food processing contaminants 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), 5‐hydroxymethylfurfural (HMF) and 2,5 dimethylfuran (DMF) are potentially both mutagenic and carcinogenic in vitro and/or in vivo, although data on DMF is lacking. The PHIP metabolite N‐hydroxy‐PhIP and HMF are bioactivated by sulfotransferases (SULTs). The substrate specificity and tissue distribution of SULTs differs between species. A single oral dose of PhIP, HMF or DMF was administered to wild‐type (wt) mice and mice expressing human SULT1A1/1A2 (hSULT mice). DNA damage was studied using the in vivo alkaline single cell gel electrophoresis (SCGE) assay. No effects were detected in wt mice. In the hSULT mice, PhIP and HMF exposure increased the levels of DNA damage in the liver and kidney, respectively. DMF was not found to be genotoxic. The observation of increased DNA damage in hSULT mice compared with wt mice supports the role of human SULTs in the bioactivation of N‐hydroxy‐PhIP and HMF in vivo. Environ. Mol. Mutagen. 56:709–714, 2015. © 2015 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc.

5-Hydroxymethylfurfural (HMF) levels in honey and other food products: effects on bees and human health

“…Mice orally administered single doses of 900 or 1300 mg/kg showed significant DNA damage of their renal cells, as detected by an alkaline single cell gel electrophoresis assay. Another furan derivative, 2,5 dimethylfuran (DMF), also causes DNA damage in the kidney and the colon [ 69 ]. In an in vitro erythropoietic micronucleus assay, rat bone marrow cells were exposed to DMF at a concentration of 0.1 mM for 1 h. The study indicated that DMF exhibits genotoxicity toward hematopoietic cells [ 53 ].…”

Risk/benefit considerations of a new formulation of wheat-based biscuit supplemented with different amounts of chia flour

“…HMF and furfural are formed as intermediate products of the Maillard reaction and furthermore, HMF is also generated by the caramelization of sugars at high temperature (Morales, 2008). Based on studies in animals, HMF is suspected to have potential genotoxic and mutagenic effects through its metabolism product sulphoxymethylfurfural (Høie et al, 2015) whereas furfural may lead to hepatotoxicity (EFSA, 2005).…”

The Toxicological Aspects of the Heat-Borne Toxicant 5-Hydroxymethylfurfural in Animals: A Review

“…In addition, in an in vitro study, a weak direct genotoxic and mutagenic effect of HMF was found at high molar concentrations [43]. Høie et al [10] examined the effects of hSULT1A1/1A2 on the genotoxicity of HMF and reported that DNA from the kidneys of hSULT mice subjected to HMF treatment showed elevated damage of DNA compared with data from control hSULT animals, but no apparent changes were seen in the kidneys of wild type mice. Moreover, it was found that HMF has a potential effect to induce sister-chromatid alteration at a level of 19.8-3808.0 µM in cells exposed for 32 h [17].…”

“…It has been also detected in cigarette smoke and chewing tobacco [4,5]. The toxicological effects of HMF have been demonstrated in several experimental animals and in cultured mammalian cells [6][7][8][9][10]. The daily human intake of HMF was reviewed by Husøy et al [11] and ranged from 30 and 150 mg/person/day, a dose much higher than that of other food heat-borne toxicants like furan and acrylamide [12,13].…”