The Butter Flavorant, Diacetyl, Forms a Covalent Adduct with 2-Deoxyguanosine, Uncoils DNA, and Leads to Cell Death

Abstract

Diacetyl (DA), a natural butter flavorant, is a causative agent for the lung disease obliterative bronchiolitis. Mutagenic properties of 1,2-dicarbonyls have previously been empirically linked to their possible interaction with DNA nucleobases. This study for the first time identifies chemically the adduct of DA with 2-deoxyguanosine. Selective reactivity of DA with 5'-TTTGTTTTT-3' over 5'-TTTTTTTTT-3' indicated its propensity to modify specifically the guanosine residue. Treatment of plasmid DNA, pBR322, with DA induced changes in electrophoretic mobility that are typical of ternary structure disruption. Such DNA nucleobase interaction of DA translated into increased apoptosis in DA-treated SH-SY5Y cells in a dose-dependent manner (IC(50) = 0.114 ± 0.0421 mM). The traditional carbonyl scavengers metformin, 2-thiobarbituric acid, and d-penicillamine protected cells from DA toxicity in proportion to their rates of reaction with DA, with d-penicillamine causing a maximal increase in the IC(50) to 5.23 ± 0.0992 mM when co-incubated with DA.

Are salty liquid food flavorings in vitro antitumor substances?

“…Likewise, Potera (2012), in a study with mice, found that diacetyl led to fibroblast proliferation in the lungs of these animals due to increased expression of genes responsible for the production of cytokines. Thus, the results obtained by More et al (2012) and Potera (2012) confirm the results obtained in this study, when the doses used stimulated a significant increase in cell division. Table III presents the number of cells in interphase and in different stages of cell division and values of the mitotic index from root meristem A. cepa cells treated with Cheddar flavoring.…”

“…Table II High doses of diacetyl are cytotoxic because of its potential to replace thymine with guanine. This change may affect the control of cell division (More et al 2012), which can explain, at least in part, the increasing in proliferating of the root meristem cells. In fact, some studies state that diacetyl might be considered a tumor activator.…”

Cytogenotoxicity of Shakes Added with Synthetic Micro Ingredients

“…The root meristem of Allium cepa L. (onion) is considered in the scientific milieu as an efficient bioassay for the evaluation of the acute toxicity at the cellular level of chemical compounds due to the reduced chromosome number (2n = 16), which favors detection of chromosomal or clastogenic alterations, mitotic spindle disturbances or aneugenic alterations, and disorders in the cell proliferation index. This test system is internationally accepted by research agencies as an assessment tool with accurate sensitivity for analysis of cytotoxicity, genotoxicity and mutagenicity of the substance of interest, since the results achieved demonstrate, in most cases, satisfactory similarity to those obtained though animal testing systems and in cell cultures Herrero et al [10], Neves et al [11], Lacerda et al [12], Tabrez et al [13]; Gomes et al [14], Oliveira et al [15]; CAMPOS & MarinMorales [16]; Moura et al [17], Santana et al [18].Therefore, the goal of this study was to evaluate the cytotoxicity and genotoxicity of diet shakes in root meristem cells of A. cepa, from three different highly commercialized brands in drugstores all over Brazil.…”

Toxicity of synthetic flavorings, nature identical and artificial, to hematopoietic tissue cells of rodents

“…In addition, More et al (2012) reported that the diluent diacetyl had the potential to replace thymine with guanine in euchromatin regions, resulting in the disruption of hydrogen and disulfide bonds in the tertiary structure of enzymes important for mitosis. Among the preservatives, potassium benzoate, sodium benzoate, potassium nitrate, are cytotoxic and genotoxic to normal cells of human peripheral blood (Mpountoukas et al, 2010;Zengin et al, 2011), boric acid, citric acid, potassium citrate and sodium citrate are cytotoxic and genotoxic to root meristem cells of A. cepa, as they caused a significant decline in the cell division rate of the examined tissue (Türkoğlu, 2007).…”

“…However, none of these regulatory agencies report in detail which compounds and concentrations are present in these substances, and to date also have not defined the Acceptable Daily Intake (ADI) and the tolerable dose limit of flavorings for each food type (Brasil, 2007;Zengin et al, 2011;More et al, 2012;Xu et al, 2015;Marques et al, 2015;Moura et al, 2016). Thus, technical regulations of FAO and FEMA mention the need for conduction of acute toxicological studies of flavorings, especially at the cellular level so as to determine whether or not the need for more detailed research on the toxic effects to organisms (Xu et al, 2015;Marques et al, 2015;Moura et al, 2016).…”