O⁶‐carboxymethylguanine DNA adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem‐rich meat

Abstract

The results suggest the haem-iron involvement for both the LPO and NOC pathway during meat digestion. Moreover, results unambiguously demonstrate that DNA adduct formation is very prone to inter-individual variation, suggesting a person-dependent susceptibility to colorectal cancer development following haem-rich meat consumption.

Synthesis and in vitro characterization of the genotoxic, mutagenic and cell-transforming potential of nitrosylated heme

“…The amount of heme found in the gut after red meat consumption depends on the following factors: the colon volume as well as the amount and type of meat ingested, with the latter showing high variations in heme content depending on the animal species under study. In the case of beef, the heme content varies from 12 to 105 µg g −1 (Mistura and Colli 2009 ; Pretorius et al 2016 ), while poultry meat contains 1.6–6 µg g −1 (Vanden Bussche et al 2014 ; Pretorius et al 2016 ), resulting in an average heme content of about 59 µg g −1 for beef and 4 µg g −1 for poultry. In order to calculate heme uptake, in which case additional influencing factors such as the bacterial uptake of heme are not considered (Yilmaz and Li 2018 ), an average colon volume of 561 ml is assumed (Pritchard et al 2014 ).…”

“…Up to now, the consumption of white meat has not been evaluated by IARC regarding its carcinogenicity and meta-analyses suggest that its consumption does not increase CRC risk (Huxley et al 2009 ; Carr et al 2016 ; Etemadi et al 2018 ). In fact, the above-mentioned evidence indicates that red meat may contain endogenous genotoxic constituents and several hypotheses have been brought forward to explain the discrepancy between red and white meat regarding their antithetical association with CRC, with one being the significantly lower heme content in white meat when compared to red meat (Lombardi-Boccia et al 2002 ; Vanden Bussche et al 2014 ; Pretorius et al 2016 ).…”

Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial

“…We recently identified dietary haem as an agent that can increase O 6 MeG adducts in the colon of mice ( 35 ) . Haem Fe-rich meat has also been shown to increase alkylated DNA adducts in an in vitro digestion system ( 47 ) . Dietary haem may also increase the production of reactive oxygen species, causing cellular toxicity and pro-mutagenic lesions ( 48 , 49 ) .…”

“…This may give an insight into the mechanisms of HRM-induced adduct formation and reasons for the associated increased risk of CRC. Furthermore, in vitro experiments have demonstrated that the formation of alkylated DNA adducts appear to depend on the microbial composition ( 47 ) . The changes that we have observed support the idea that the increases in stool SCFA levels and the associated protection against dietary HRM-mediated colorectal tissue damage that have occurred in response to dietary RS treatment are at least partly mediated by the gut microbiota, through both cleavage of the esterified butyrate and fermentation of the RS substrate.…”

Effect of diet and gut environment on the gastrointestinal formation of N -nitroso compounds: A review

“…Because heme iron is much more abundant in red meat than in white meat and fish, recent studies on humans have clearly indicated that red meat is directly and dose-dependently associated with colonal NOC formation and subsequent colonic formation of the NOC-specific DNA adduct (DNA adduct O 6 -carboxymethyl guanine) that causes colorectal cancer [12,53] (Table 2). In addition to contributing to NOC formation, heme iron was reported in a rat experiment to have peroxidase activity and generated carcinogenic lipid peroxidation end-products such as aldehyde [6], suggesting that heme iron-mediated lipid peroxidation could be another important mechanism to promote colorectal cancer [15,76].…”