Living organisms are continuously exposed to a myriad of DNA damaging agents that can impact health and modulate disease-states. However, robust DNA repair and damage-bypass mechanisms faithfully protect the DNA by either removing or tolerating the damage to ensure an overall survival. Deviations in this fine-tuning are known to destabilize cellular metabolic homeostasis, as exemplified in diverse cancers where disruption or deregulation of DNA repair pathways results in genome instability. Because routinely used biological, physical and chemical agents impact human health, testing their genotoxicity and regulating their use have become important. In this introductory review, we will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue. Environ. Mol. Mutagen. 58:235-263, 2017. © 2017 Wiley Periodicals, Inc.

Mechanisms of DNA damage, repair, and mutagenesis.

The pressing issue to feed the increasing world population has created a demand to enhance food production, which has to be cheaper, but at the same time must meet high quality standards. Taste, appearance, texture, and microbiological safety are required to be preserved within a foodstuff for the longest period of time. Although considerable improvements have been achieved in terms of food additives, some are still enveloped in controversy. The lack of uniformity in worldwide laws regarding additives, along with conflicting results of many studies help foster this controversy. In this report, the most important preservatives, nutritional additives, coloring, flavoring, texturizing, and miscellaneous agents are analyzed in terms of safety and toxicity. Natural additives and extracts, which are gaining interest due to changes in consumer habits are also evaluated in terms of their benefits to health and combined effects. Technologies, like edible coatings and films, which have helped overcome some drawbacks of additives, but still pose some disadvantages, are briefly addressed. Future trends like nanoencapsulation and the development of "smart" additives and packages, specific vaccines for intolerance to additives, use of fungi to produce additives, and DNA recombinant technologies are summarized.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1541-4337.12065

Adding Molecules to Food, Pros and Cons: A Review on Synthetic and Natural Food Additives

In a time where the public is more aware and interested with what they eat, natural additives have been gaining interest both from the food industries and the consumers. Some studies show that consumers prefer food prepared with natural additives rather than chemical ones, due to health reasons. Although quite promising, natural additives still face some drawbacks and limitations as well as conflicting information. In this manuscript, the most important natural additives are overviewed, as well as their use, benefits and risks. The future of these molecules along with new types of additives is also summarized.

/pdf/natural-food-additives-quo-vadis-2srr702w1o.pdf

Natural food additives: Quo vadis?

The evolution of drug resistance is an important process that affects clinical outcomes. Resistance to fluconazole, the most widely used antifungal, is often associated with acquired aneuploidy. Here we provide a longitudinal study of the prevalence and dynamics of gross chromosomal rearrangements, including aneuploidy, in the presence and absence of fluconazole during a well-controlled in vitro evolution experiment using Candida albicans, the most prevalent human fungal pathogen. While no aneuploidy was detected in any of the no-drug control populations, in all fluconazole-treated populations analyzed an isochromosome 5L [i(5L)] appeared soon after drug exposure. This isochromosome was associated with increased fitness in the presence of drug and, over time, became fixed in independent populations. In two separate cases, larger supernumerary chromosomes composed of i(5L) attached to an intact chromosome or chromosome fragment formed during exposure to the drug. Other aneuploidies, particularly trisomies of the smaller chromosomes (Chr3–7), appeared throughout the evolution experiment, and the accumulation of multiple aneuploid chromosomes per cell coincided with the highest resistance to fluconazole. Unlike the case in many other organisms, some isolates carrying i(5L) exhibited improved fitness in the presence, as well as in the absence, of fluconazole. The early appearance of aneuploidy is consistent with a model in which C. albicans becomes more permissive of chromosome rearrangements and segregation defects in the presence of fluconazole.

/pdf/acquisition-of-aneuploidy-provides-increased-fitness-during-2w8bq7ongr.pdf

Acquisition of aneuploidy provides increased fitness during the evolution of antifungal drug resistance.

Modern analytical techniques can determine a multitude of fungal metabolites contaminating food and feed. In addition to known mycotoxins, for which maximum levels in food are enforced, also currently unregulated, so-called “emerging mycotoxins” were shown to occur frequently in agricultural products. The aim of this review is to critically discuss the relevance of selected emerging mycotoxins to food and feed safety. Acute and chronic toxicity as well as occurrence data are presented for enniatins, beauvericin, moniliformin, fusaproliferin, fusaric acid, culmorin, butenolide, sterigmatocystin, emodin, mycophenolic acid, alternariol, alternariol monomethyl ether, and tenuazonic acid. By far not all of the detected compounds are toxicologically relevant at their naturally occurring levels and are therefore of little or no health concern to consumers. Still, gaps in knowledge have been identified for several compounds. These gaps should be closed by the scientific community in the coming years to allow a pr...

http://pubs.acs.org/doi/pdf/10.1021/acs.jafc.6b03413

Emerging Mycotoxins: Beyond Traditionally Determined Food Contaminants

The evaluation of the genotoxicity of two food preservatives: Sodium benzoate and potassium benzoate

Does potassium sorbate induce genotoxic or mutagenic effects in lymphocytes

Genotoxicity of monosodium glutamate.

The aim of this study was to investigate the genotoxic risk to workers occupationally exposed to coal combustion products in Afsin-Elbistan A power plant, located in south-eastern Turkey. We analysed chromosomal aberrations (CAs), polyploidy, sister-chromatid exchanges (SCEs), and micronuclei (MN) in 48 male workers without a history of smoking, tobacco chewing, or alcohol consumption. The results were compared with a control group of 30 healthy male individuals without exposure to any known genotoxic agents. The mean frequencies of CA, polyploidy, SCEs ( P P U -test. Spearman's rho correlation analysis revealed a significant increase in the frequency of CA and MN with increasing years of exposure ( P P  > 0.05). The data obtained from this study clearly showed chromosomal hazard in the peripheral lymphocytes of workers exposed to coal combustion products in Afsin-Elbistan A power plant for several years. This cytogenetic damage might be attributed to the cumulative effects of several substances due to chemical complexity of the coal ash and gaseous emissions rather than a specific substance.

Cytogenetic damage in workers from a coal-fired power plant.

The genotoxic effects of the fungicide afugan were analysed by measuring chromosomal aberrations (CAs), sister chromatid exchange (SCE) and micronuclei (MN) in cultured human peripheral lymphocytes Concentrations of 25, 5, 10 and 20 μg/ml of afugan were used during 24 and 48 h Afugan significantly increased the frequency of CAs at 5, 10 and 20 μg/ml concentrations during a 48 h treatment period A significant increase was observed for induction of SCE and MN at all treatments compared with the negative control A significant dose–response correlation was found in all tests Afugan did not affect the replicative index (RI), however it significantly decreased the mitotic index (MI) at all treatment concentrations except 25 μg/ml, and at both treatment times The present results indicate that afugan is clastogenic and cytotoxic to cultured human lymphocytes

Deniz Yüzbaşıoğlu

Papers

The evaluation of the genotoxicity of two food preservatives: Sodium benzoate and potassium benzoate

Does potassium sorbate induce genotoxic or mutagenic effects in lymphocytes

Genotoxicity of monosodium glutamate.

Cytogenetic damage in workers from a coal-fired power plant.

Clastogenicity of the fungicide afugan in cultured human lymphocytes