Genotoxicity of silver nanoparticles

Silver nanoparticles (AgNPs) are widely used in diverse sectors such as medicine, food, cosmetics, household items, textiles and electronics. Given the extent of human exposure to AgNPs, information about the toxicological effects of such products is required to ensure their safety. For this reason, we performed a bibliographic review of the genotoxicity studies carried out with AgNPs over the last six years. A total of 43 articles that used well-established standard assays (i.e., in vitro mouse lymphoma assays, in vitro micronucleus tests, in vitro comet assays, in vivo micronucleus tests, in vivo chromosome aberration tests and in vivo comet assays), were selected. The results showed that AgNPs produce genotoxic effects at all DNA damage levels evaluated, in both in vitro and in vivo assays. However, a higher proportion of positive results was obtained in the in vitro studies. Some authors observed that coating and size had an effect on both in vitro and in vivo results. None of the studies included a complete battery of assays, as recommended by ICH and EFSA guidelines, and few of the authors followed OECD guidelines when performing assays. A complete genotoxicological characterization of AgNPs is required for decision-making

Pediatric Meningosarcoma: Clinical Evolution and Genetic Instability

This report presents a female diagnosed with a frontoparietal interhemispheric meningosarcoma who, parallel to the clinical worsening, revealed an increase in the genetic instability (in bleomycin cultures) and the complexity of the karyotypes, with the acquisition of a clonal deletion of 17p13 (the locus for the TP53 tumor suppressor gene). The genetic findings of this patient suggest that the increased genetic instability could contribute to tumor progression as well as to treatment resistance, possibly in the background of the clonal deletion of TP53

Nonclonal Chromosomal Aberrations Induced by Anti-Tumoral Regimens in Childhood Cancer: Relationship with Cancer-Related Genes and Fragile Sites

Cytogenetic studies were performed on 80 pediatric cancer patients to observe the chromosomal damage, both quantitative and qualitative, induced by chemotherapy. Peripheral blood lymphocytes (PBL) (n = 127) were obtained at diagnosis, during treatment, at remission, and at relapse, and chromosome analysis performed utilizing G-banding standard procedures. The results show a significant increase in the number of altered karyotypes (P = 0.03) in the samples during treatment, returning to values that were similar to those at diagnosis at 2-year remission. Most of the chromosomal aberrations (CA) detected during the chemotherapy regimens were nonclonal, unbalanced (75%), and involved chromosomes 1, 3, 5, 6, 11, 12, 16, and 17 most frequently. There was also a marked increase of CA in samples at relapse with very similar features (type and distribution) to those detected during treatment. There was a good correlation between the chromosomal breakpoints in our series and fragile sites (58%), oncogene (75%), and tumor suppressor gene (33%) loci described in the literature. The results obtained suggest that cytostatic drugs induce a transient increase in chromosome fragility occurring at several cancer-associated breakpoints

Ochratoxin A kinetics: a review of analytical methods and studies in rat model

Ochratoxin A (OTA) is a thermostable mycotoxin that contaminates a great variety of foodstuffs. It is nephrotoxic in all of the mammalian species tested, being the pig the most sensitive one; among rodents, rats are the most susceptible to OTA carcinogenicity. Kinetics, by studying the absorption, distribution, metabolism and excretion of xenobiotics, is an important tool for the extrapolation of animal toxicity data. The most important kinetic studies performed with OTA in rats have been reviewed, together with the different methods used for OTA quantification in biological matrices. Thirteen studies in Wistar, Sprague-Dawley or F344 rats, using radiolabeled OTA or TLC, HPLC-FLD or HPLC-MS have been summarized. Very often methods validated for food have been directly applied to tissues. Strain, sex and age differences have been detected but the interpretation is difficult due to the different experimental conditions, and the connection of the several factors that may account for these differences

An approach to the toxicity and toxicokinetics of aflatoxin B1 and ochratoxin A after simultaneous oral administration to fasted F344 rats

Humans are exposed to the hepatotoxic aflatoxin B1 (AFB1) and nephrotoxic ochratoxin A (OTA) through diet. However, kinetic and toxicological data after their co-administration are scarce. In this study, a single oral dose of AFB1 (0.25mg/kg bw)+OTA (0.5mg/kgbw) was administered to fasted F344 rats. Blood, liver and kidney were harvested at different timepoints for mycotoxins quantification, relative weight calculation, clinical biochemistry and histopathology analysis. Toxicity parameters pointed to acute toxicity in liver due to AFB1. No remarkable toxicity was observed in kidneys or immunological organs. Maximum observed concentrations in plasma (C(max)) were at 10min and 2h for AFB1 and OTA, respectively. AFB1 plasma concentration could indicate a rapid absorption/ metabolism of the mycotoxin; and AFB1 liver and kidney concentrations were lower than LOQ and LOD, respectively. For OTA, C(max) was 4326.2μg/L in plasma. In kidney and liver C(max) was reached at 8h and concentrations were very similar between both organs at all timepoints. Due to the low levels of AFB1, the effect of OTA on AFB1 kinetics could not be assessed. However, AFB1 seems not to affect OTA kinetics, as its profile seems very similar to kinetic studies performed only with OTA in similar conditions

In vitro mutagenicity assessment of fried meat-based food from mass catering companies

The current article aimed to evaluate the in vitro mutagenicity of ten fried meat-based food extracts obtained from different catering companies from Navarra (Spain). A miniaturized 6-well version of the Ames test in Salmonella typhimurium TA98, and the in vitro micronucleus test (OECD TG 487) in TK6 cells were performed. None of the ten extracts of fried meat-based food induced gene mutations in S. typhimurium TA98 with or without metabolic activation, but five induced chromosomal aberrations after 24 h treatment of TK6 without metabolic activation. More studies are needed to check the biological relevance of these in vitro studies

Practices of deep-frying processes among food handlers in social food services in Navarra, Spain

Deep frying is one of the most used worldwide methods in food preparation, but controlling the oil quality (temperature and formation of polar compounds) is crucial. The main objective of this work was to assess the practices of food handlers with regard to the frying processes in social food services located in Navarra (a region of northern Spain). The study was performed in two phases: in the first one, a self-administrable questionnaire regarding the usual practices on food deep-frying processes was sent to the food services through the main social catering companies of Navarra participating in the study. In the second one, in situ monitoring of the frying practices was performed as verification tools of frying practices reported by food services and to check the oil quality. Almost half of the fryers exceeded the maximum recommended temperature to avoid the formation of toxic compounds (175 ◦C). Despite only one the fryers exceeded the maximum limit of polar compounds established by current Spanish regulation, the obtained values indicated that the oil had begun to degrade in 20% of the fryers. Oil temperature is an important factor that affects the quality of the oil. In addition, significant differences were found between the different frequencies of change or types of oils. We have noticed a lack of knowledge in relation to the risks associated to the bad management of frying oil. Therefore, it would be desirable to improve food handlers training in relation to this matter. Defining a periodic frequency of oil change according to its use and periodic controls of temperature and polar compounds (as part of the Hazard Analysis and Critical Control Point system), could be adequate tools to improve management of frying oil in food services

Quantification of ochratoxin A and five analogs in Navarra red wines

Ochratoxin A (OTA), B (OTB) and their methyl (MeOTA, MeOTB) and ethyl (OTC, EtOTB) esters were evaluated in 51 red wine samples from Navarra (Spain). Detectable levels of OTA and OTB were found in 100% of the samples, and 71% showed the presence of OTC. The six ochratoxins appeared simultaneously in 18% of the samples. Results indicated that OTC is hydrolyzed to OTA in red wine. Therefore, ochratoxin intake from wine can be underestimated when only assessed by OTA analysis. Analyzed Navarra wines are scarcely contaminated with ochratoxins and their contribution to human intake is low, with the worst case being 4.7% and 6.6% of the provisional tolerable weekly intake (PTWI) for OTA and for the sum of ochratoxins, respectively. No significant differences were generally found between vintages. With the exception of OTA, no significant differences were observed between organic and traditional farming. Levels of ochratoxins were positively correlated with temperature and inversely correlated with humidity and rainfall

Comet assay modifications for its application in food safety

Information on genotoxicity is of a key importance for the toxicological characterisation of different compounds. In this vein, and due to its various advantages, the comet assay is currently included in the genotoxicity testing strategy used in the food safety area. However, improvement points of particular interest have been identified. Thereby, the main objective of the present work was to evaluate some critical points of the comet assay, such as the time of lysis, in vitro, and the methodology used in the freezing/thawing procedures of tissue samples, their stability and the application of the Fpg-modified assay, in vivo. In addition, the in vivo comet assay was applied to frozen kidney samples obtained in a previous repeated-dose toxicity study of the food contaminant ochratoxin A. Finally, the knowledge derived from these objectives resulted in the development of standard operating procedures for both the in vitro and in vivo comet assays, which could be applied in good laboratory practice studies