Genotoxic Risk Research Articles

Bacterial Composition, Genotoxicity, and Cytotoxicity of Fecal Samples from Individuals Consuming Omnivorous or Vegetarian Diets.

This study analyzes the composition of viable fecal bacteria and gut toxicology biomarkers of 29 healthy volunteers, who followed omnivorous, lacto-ovo-vegetarian, or vegan diets. In particular, the research was focused on the prevalence of some representative viable bacteria from the four dominant phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria) commonly present in human feces, in order to evaluate the relationship between microorganisms selected by the habitual dietary patterns and the potential risk due to fecal water (FW) genotoxicity and cytotoxicity, considered as biomarkers for cancer risk and protective food activity. The relative differences of viable bacteria among dietary groups were generally not statistically significant. However, compared to omnivores, lacto-ovo-vegetarians showed low levels of total anaerobes. Otherwise, vegans showed total anaerobes counts similar to those of omnivores, but with lower number of bifidobacteria and the highest levels of bacteria from the Bacteroides–Prevotella genera. FW genotoxicity of lacto-ovo-vegetarians resulted significantly lower either in relation to that of omnivores and vegans. Lacto-ovo-vegetarians also showed the lowest levels of cytotoxicity, while the highest were found for vegans. These results highlighted that lacto-ovo-vegetarian diet was particularly effective in a favorable modulation of microbial activity, thus contributing to a significant reduction of the genotoxic and cytotoxic risk in the gut.

Kinetics, mechanisms, and influencing factors on the treatment of haloacetonitriles (HANs) in water by two household heating devices

Haloacetonitriles (HANs) are a group of nitrogenous disinfection by-products (DBPs) commonly found in treated water with potential carcinogenic, cytotoxic, and genotoxic risks. In order to control HANs and understand their real intake levels by people via drinking water, this study evaluated a list of structural, operational, and environmental factors affecting the treatment of HANs by two domestic heating devices, i.e., an electric boiler and a microwave oven. Results show that the concentrations of HANs decreased exponentially over time with increasing temperature, water turbulence, and bubbles, and the phenomena were most likely due to a combined effect of volatilization and hydrolysis. Among HANs, the lability increased with increasing halogenation degrees (i.e., tri- > di- > mono- HANs) yet decreasing halogen molecular weights (i.e., Cl- > Br- > I- HANs); such trends were well captured by quantitative structure activity relationship models (R2 = 0.99). Operational factors played critical roles in controlling HANs too, including the rate of heating, water volume, water temperature at time of pouring, cooling method, and capping condition, suggesting that people could benefit from proper handling methods and procedures. In addition, HANs added to tap water exhibited higher removals than those added to ultrapure water, probably because of the presence of free chlorine in tap water.

Cellular Homeostasis and Antioxidant Response in Epithelial HT29 Cells on Titania Nanotube Arrays Surface.

Cell growth and proliferative activities on titania nanotube arrays (TNA) have raised alerts on genotoxicity risk. Present toxicogenomic approach focused on epithelial HT29 cells with TNA surface. Fledgling cell-TNA interaction has triggered G0/G1 cell cycle arrests and initiates DNA damage surveillance checkpoint, which possibly indicated the cellular stress stimuli. A profound gene regulation was observed to be involved in cellular growth and survival signals such as p53 and AKT expressions. Interestingly, the activation of redox regulator pathways (antioxidant defense) was observed through the cascade interactions of GADD45, MYC, CHECK1, and ATR genes. These mechanisms furnish to protect DNA during cellular division from an oxidative challenge, set in motion with XRRC5 and RAD50 genes for DNA damage and repair activities. The cell fate decision on TNA-nanoenvironment has been reported to possibly regulate proliferative activities via expression of p27 and BCL2 tumor suppressor proteins, cogent with SKP2 and BCL2 oncogenic proteins suppression. Findings suggested that epithelial HT29 cells on the surface of TNA may have a positive regulation via cell-homeostasis mechanisms: a careful circadian orchestration between cell proliferation, survival, and death. This nanomolecular knowledge could be beneficial for advanced medical applications such as in nanomedicine and nanotherapeutics.

Study of anti-inflammatory and analgesic properties of 3-benzoyl-propionic acid

Inflammation is an attempt by the body to remove noxious stimuli and initiate thus a cascade of responses in order to promote healing. There are a variety of inflammatory mechanisms involved in infections, chronic diseases and other tissue damage. Understanding these mechanisms and the search for new anti-inflammatory drugs with greater specificity and fewer side effects, underlying the development and improvement of new protocols and standardization of experimental inflammatory models to understand better these issues. The aim of this study was to evaluate the anti-inflammatory and analgesic activity of 3-benzoyl-propionic acid (3BPA) and its potential toxicological effect. To test the 3BPA as new anti-inflammatory and analgesic drug, the use carrageenan air pouch model 1% by in vitro model of cell culture to test genocytotoxicity. In the in vitro model the 3BPA presented low level of genotoxic and low cytotoxicity risk, shown by comet assay and no damage to the plasma membrane by hemolytic test erythrocytes. In the study of anti-inflammatory activityin vivo by the air pouch method were conducted nitrite dose trials, PGE2 levels and cell migration. To verify analgesic effects of 3BPA drugin vivo tests of abdominal contortions induced by acetic acid and formalin were performed. Regard to the anti-inflammatory activity, 3BPA showed intense activity shown in marked reduction of cell migration and levels of NO, with large populations of neutrophils and reduction of PGE 2 values at a dose of 0.5mg/kg. In studies of antinociceptive activity, 3BPA reduced the number of writhes and the time lick the neurogenic and inflammatory phases of the formalin test. The results of this study also advanced substantially with respect to anti-inflammatory and analgesic properties of 3BPA by providing evidence of their likely mechanism of action, through the evaluation of antinociceptive activity, as well as the anti-inflammatory activity in vitro and in vivo, where the 3BPA showed no genotoxic effect.

Micronucleus Assay in Urothelial Cells in Cancer Cervix.

Cancer ranks third among the ten leading global causes of death. To evaluate the genotoxic risks, observed as DNA damages, can be assessed by Micronucleus (MN) test. To identify the occurrence of MN in normal and cancer cervix and find the correlation between MN and stage of cancer. A total of 60 females were included in the study and visual examination of the cervix was done. Based on the examination two groups were formed: A- Normal cervix (n-23) and B- Presence of erosion or growth or ulcer etc., in cervix (n-37). Midstream urine sample was collected and centrifuged from the cases after getting the informed consent. Slides were prepared from the pellet, were fixed in methanol, glacial acetic acid fixative and stained with Giemsa and May Grunwald stain. Statistical analysis was done by student's t-test and chi-square test. A linear association was noted between the mean MN count and cancer cervix stage. Almost 18.2% of the Group A cases had significant MN count. Sensitivity and specificity of MN count in Group A was 83.8% and 82.6% respectively. The efficiency was 83.3%. A statistically significant MN count was seen in the different stages of cancer cervix. There are cases who had normal findings on visual inspection of cervix but with significant MN count are prone for malignant transformation. MN assay is an easy, non-invasive, cost-effective method and can be used as a screening test for a large population.

Magnesium stearate, a widely-used food additive, exhibits a lack of in vitro and in vivo genotoxic potential.

Magnesium stearate is widely used in the production of dietary supplement and pharmaceutical tablets, capsules and powders as well as many food products, including a variety of confectionery, spices and baking ingredients. Although considered to have a safe toxicity profile, there is no available information regarding its potential to induce genetic toxicity. To aid safety assessment efforts, magnesium sulfate was evaluated in a battery of tests including a bacterial reverse mutation assay, an in vitro chromosome aberration assay, and an in vivo erythrocyte micronucleus assay. Magnesium stearate did not produce a positive response in any of the five bacterial strains tested, in the absence or presence of metabolic activation. Similarly, exposure to magnesium stearate did not lead to chromosomal aberrations in CHL/IU Chinese hamster lung fibroblasts, with or without metabolic activation, or induce micronuclei in the bone marrow of male CD-1 mice. These studies have been used by the Japanese government and the Joint FAO/WHO Expert Committee on Food Additives in their respective safety assessments of magnesium stearate. These data indicate a lack of genotoxic risk posed by magnesium stearate consumed at current estimated dietary exposures. However, health effects of cumulative exposure to magnesium via multiple sources present in food additives may be of concern and warrant further evaluation.

Single Low-Dose Ionizing Radiation Induces Genotoxicity in Adult Zebrafish and its Non-Irradiated Progeny.

This study investigated to what extent a single exposure to low doses of ionizing radiation can induce genotoxic damage in irradiated adult zebrafish (Danio rerio) and its non-irradiated F1 progeny. Four groups of adult zebrafish were irradiated with a single dose of X-rays at 0 (control), 100, 500 and 1000mGy, respectively, and couples of each group were allowed to reproduce following irradiation. Blood of parental fish and whole-body offspring were analysed by the comet assay for detection of DNA damage. The level of DNA damage in irradiated parental fish increased in a radiation dose-dependent manner at day 1 post-irradiation, but returned to the control level thereafter. The level of DNA damage in the progeny was directly correlated with the parental irradiation dose. Results highlight the genotoxic risk of a single exposure to low-dose ionizing radiation in irradiated individuals and also in its non-irradiated progeny.

Genotoxic risk of ethyl-paraben could be related to telomere shortening.

The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines. We observed a significant increase in genotoxic damage using the Mouse Lymphoma Assay and in vitro micronucleus (MN) tests in the L5178Y cell line in the presence of S9 only after a short exposure. A high frequency of MN was observed in the TK6 cells after a short exposure (3 h) in the presence of S9 and a long exposure (26 h) without S9. We found significant increases in the MN frequency and induced chromosomal aberrations in the lymphocytes of only one donor after ethyl-paraben exposure in the presence of S9 after a short exposure. Cytogenetic characterization of the paraben-treated cells demonstrated telomere shortening associated with telomere loss and telomere deletions in L5178Y and TK6 cells and lymphocytes of the paraben sensitive-donor. In a control cohort of 68 human lymphocytes, telomere length and telomere aberrations were age-dependent and showed high inter-individual variation. This study is the first to link telomere shortening and the genotoxic effect of ethyl paraben in the presence of S9 and raises the possibility that telomere shortening may be a proxy for underlying inter-individual sensitivity to ethyl-paraben. Copyright © 2016 John Wiley & Sons, Ltd.

Comparative evaluation of genotoxic effects of lead and red color iron oxide in rat colon

Lead is one of many widely used heavy metals in consumer products, such as red colour paint, even though lead has a diverse array of biologically harmful effects. Red color iron oxide pigments have emerged to reduce the risk of lead toxicity and replace leadbased red pigments. Despite of the existence of numerous studies on the chemical and physical properties of iron oxide, studies on the biological safety are required. Here, we investigated the genotoxic effect of lead exposure in colon tissue by performing an acute test and subacute test utilizing the comet assay and micronucleus assay. We observed that lead-induced genotoxicity was generally higher than iron oxide-induced genotoxicity, leading us to conclude that iron oxide has a generally lower genotoxic risk than lead. Through our results, we have verified that iron oxide is an acceptable alternative material of lead-based pigments. We hope that our study will form the basis for further research on the safety evaluation of other substitutions of heavy metal based materials.

Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model.

Isothiocyanates are the most intensively studied breakdown products of glucosinolates from Brassica plants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the genotoxic potential of nitriles was found to be comparable to isothiocyanates. DNA damage was persistent over a certain time period and CYP2E1-overexpression further increased the genotoxic potential of the nitriles. Based on actual in vitro data, no indications are given that food-borne nitriles could be relevant for cancer prevention, but could pose a certain genotoxic risk under conditions relevant for food consumption.

Mutagenic, genotoxic and bioaccumulative potentials of tannery effluents in freshwater fishes of River Ganga

ABSTRACTThe tannery industries are the reason of major environmental concerns as they release toxic heavy metals, like chromium, in rivers posing risks of genotoxicity and mutagenicity in aquatic organism and indirectly in humans through food chain. In the present analysis, the freshwater inhabitant fishes of River Ganges, viz., Labeo calbasu, Puntius sophore, and Mystus vittatus, were examined for assessing the genotoxic, mutagenic, and bioaccumulative potentials of tannery effluents. For genotoxicity assessment, the blood and gill samples of fishes prevailed from polluted sites of River Ganges adjoining Kanpur city were utilized for comet assay and micronucleus test. The present investigation revealed the presence of significantly (p < 0.05) higher micronuclei induction and % tail DNA in erythrocytes and gill cells of the fishes collected from the polluted sites. The bioaccumulation studies revealed chromium concentration in muscle (0.89 µg/g) and gill tissues (0.24 µg/g) of L. calbasu; muscle (0.44 µg/g) and gills (1.23 µg/g) of P. sophore; and muscle (0.9617 µg/g) and gills (0.3628 µg/g) of M. vittatus, quite higher than the permissible limits of the World Health Organization. Consequently, the present study indicates strongly that River Ganges is contaminated with harmful tannery pollutants causing genotoxicity and mutagenicity in freshwater fishes.

Assessment of genotoxicity in female agricultural workers exposed to pesticides

Objective: This study was designed to determine the genotoxic effect of exposure to a mixture of pesticides in 106 female agricultural workers employed in cotton fields from India.Methods: Comet, micronucleus and chromosomal aberrations tests were carried out in peripheral blood lymphocytes. Micronucleus test was also performed in buccal epithelial cells. Levels of antioxidant enzymes, RBC acetylcholinesterase and hematological parameters were analyzed in the blood samples of the study subjects.Results: The results indicated significant DNA damage, increased frequency of micronuclei and chromosomal aberrations in the exposed subjects (p < 0.05). The levels of antioxidant enzymes were significantly lowered and the rate of lipid peroxidation was elevated in the exposed subjects.Conclusion: The outcome of the study revealed an increased risk of genotoxicity and health implications in female agricultural workers.

Viral Vectors: The Road to Reducing Genotoxicity.

Viral vector use in gene therapy has highlighted several safety concerns, including genotoxic events. Generally, vector-mediated genotoxicity results from upregulation of cellular proto-oncogenes via promoter insertion, promoter activation, or gene transcript truncation, with enhancer-mediated activation of nearby genes the primary mechanism reported in gene therapy trials. Vector-mediated genotoxicity can be influenced by virus type, integration target site, and target cell type; different vectors have distinct integration profiles which are cell-specific. Non-viral factors, including patient age, disease, and dose can also influence genotoxic potential, thus the choice of test models and clinical trial populations is important to ensure they are indicative of efficacy and safety. Efforts have been made to develop viral vectors with less risk of insertional mutagenesis, including self-inactivating (SIN) vectors, enhancer-blocking insulators, and microRNA targeting of vectors, although insertional mutagenesis is not completely abrogated. Here we provide an overview of the current understanding of viral vector-mediated genotoxicity risk from factors contributing to viral vector-mediated genotoxicity to efforts made to reduce genotoxicity, and testing strategies required to adequately assess the risk of insertional mutagenesis. It is clear that there is not a 'one size fits all' approach to vector modification for reducing genotoxicity, and addressing these challenges will be a key step in the development of therapies such as CRISPR-Cas9 and delivery of future gene-editing technologies.

Safety evaluation of styrax liquidus from the viewpoint of genotoxicity and mutagenicity

Ethnopharmacological relevanceStyrax liquidus is a resinous exudate (balsam) obtained from the wounded trunk of the Liquidambar orientalis Mill. (Hamamelidaceae). Styrax has been used for treatment of various ailments in Turkish folk medicine such as skin problems, peptic ulcers, nocturnal enuresis, parasitic infections, antiseptic or as expectorant. Aim of studyIn spite of frequent use of styrax in Turkish folk medicine as well as once as a stabilizer in perfumery industry, negative reports have been noticed by the international authority for restriction its use based on some limited evidences from an in vitro study. The aim of the present study was to evaluate the genotoxic and cytotoxic potential of styrax and its ethanolic extract using in vivo and in vitro assays, as well as an antimutagenic assay and also to determine its phenolic constituents with chromatographic analysis. Materials and methodsIn vitro mutagenicity and antimutagenicity of styrax and its ethanolic extract were evaluated by Ames test performed on Salmonella TA98 and TA100 strains with and without metabolic activation (10– 30,000µg/plate). The genotoxicity was also studied in vivo by chromosomal aberrations assay on bone marrow of Balb C mice with different its concentrations (500–2000mg/kg body weight). Cytotoxicity has been evaluated by the MTT assay using L929 cell line. Its phenolic constituents were determined by HPLC analysis. ResultsGenotoxicological investigations of styrax or its ethanolic extract showed that none of the tested concentrations induced a significant increase in the revertant number of TA98 and TA100 strains with or without metabolic activation, indicating no mutagenicity to the tested strains. Also results indicated that up to 2000mg/kg body weight, styrax is not genotoxic in mammalian bone marrow chromosome aberration test in vivo. In cytotoxicity study, the IC50 values of styrax and its ethanolic extract were found to be 50.22±1.80 and 59.69±11.77µg/mL, respectively. Among the studied reference standards the major phenolic acids in styrax balsam was found to be p-coumaric acid (2.95mg/g), while in its ethanolic extract not only p-coumaric acid (11.46mg/g), but also gallic acid (1.60mg/g) were found to the main components. ConclusionThe findings of the present study provide scientific basis to the safety of styrax from the viewpoint of genotoxicity risk, and in fact, it was found to be beneficial against genotoxicity.

Effect of low-dose X-ray irradiation on micronucleus formation in human embryo, newborn and child cells

Purpose: It is well known that a high-dose of ionizing radiation is sufficient to break DNA strands, which leads to elevated genotoxic risks; however, the risks associated with low doses of ionizing radiation remain unclear. In addition, there is little data about the effect of low-dose ionizing radiation on human-derived embryo, newborn and child cells. We investigated the frequency of micronucleus (MN) formation in these cells to understand the genotoxic effects of ionizing radiation.Materials and methods: We irradiated the cells with X-rays from 0.02–2 Gy at a rate of 0.0635 Gy/min. After irradiation, we investigated the effect of low-dose X-ray irradiation on cellular viability and frequency of MN formation.Results: Increases in MN formation were largely dose-dependent; however, there were no differences between controls and doses lower than 0.2 Gy, except in KMST-6 human transformed embryo cells.Conclusion: We could not detect an obvious effect of low-dose X-ray irradiation at doses lower than 0.1 Gy. The embryonic cells were more sensitive to X-ray irradiation than newborn and child cells. The threshold for X-ray-induced MN formation appears to be in the range of 0.05–0.1 Gy in cultured human embryo, newborn and child cells.

Anaesthetic and genotoxic effect of medicinal plant extracts in gilthead seabream (Sparus aurata L.)

Anaesthetic properties and potential genotoxicity of six essential oils extracted from the medicinal plants Origanum vulgare, Eugenia aromatica, Aloysia triphylla, Melaleuca alternifolia, Juniperus communis, Cinnamomum zeylanicum, are presently assessed in gilthead seabream. Essential oils are an alternative option for fish anaesthesia, which is necessary in order to ensure welfare under intensively reared conditions. Their anaesthetic efficacy was assessed in comparison with chemical agents, by monitoring fish behavior throughout the anaesthesia and recovery stages, while the post-treatment mortality rate was also recorded. Genotoxicity was evaluated using the single cell gel comet assay in vitro and in vivo. DNA migration (tail moment) and the percentage of cells with increased level of DNA damage in hepatocytes were assessed. All essential oils proved to qualify as anaesthetic agents achieving deep narcosis and behavioural recovery. Essential oils indicated higher efficiency compared to chemicals, mitigating the side-effects that are often associated with synthetic substances. E. aromatic, O. vulgare and A. triphylla induced genotoxic effects at applied doses. However, as genotoxicity is dose dependent and most essential oils usually devoid of long-term genotoxic risk, lower anaesthetic doses have to be tested in order to be proposed for commercial use in aquaculture species. M. alternifolia and J. communis did not induced genotoxicity, maintaining DNA damage at control group level. Finally, C. zeylanicum was evaluated as equal competent anaesthetic agent satisfying the criteria of the ideal anaesthetic, reducing DNA strand breakage and indicating anti-stress, anti-genotoxic and geno-protective effect. Statement of relevance•Genotoxicity of anaesthetic agents used for fish anaesthesia is an important issue in aquaculture production. As aquaculture fish are intended for human consumption, essential oils are an alternative option for anaesthesia, providing low cost, easy accessibility, efficacy and environmental safety.•Due to the fact that essential oils may display dose-dependent toxicity, research on their genotoxic effect is very important before they are suggested for commercial use in aquaculture.•The essential oils extracted from medicinal plants Origanum vulgare, Eugenia aromatica, Aloysia triphylla, Melaleuca alternifolia, Juniperus communis, Cinnamomum zeylanicum have never been assessed for their anaesthetic and genotoxic effect in seabream. Furthermore, comet assay is considered as an innovative and validated molecular assay for reliable detection of genotoxicants.

Evaluating genotoxic risks in Brazilian public health agents occupationally exposed to pesticides: a multi-biomarker approach.

This is the first study demonstrating genotoxic effects and whole transcriptome analysis on community health agents (CHAs) occupationally exposed to pesticides in Central Brazil. For the transcriptome analysis, we found some genes related to Alzheimer's disease (LRP1), an insulin-like growth factor receptor (IGF2R), immunity genes (IGL family and IGJ), two genes related to inflammatory reaction (CXCL5 and CCL3), one gene related to maintenance of cellular morphology (NHS), one gene considered to be a strong apoptosis inductor (LGALS14), and several transcripts of the neuroblastoma breakpoint family (NBPF). Related to comet assay, we demonstrated a significant increase in DNA damage, measured by the olive tail moment (OTM), in the exposed group compared to the control group. Moreover, we also observed a statistically significant difference in OTM values depending on GSTM1 genotypes. Therefore, Brazilian epidemiological surveillance, an organization responsible for the assessment and management of health risks associated to pesticide exposure to CHA, needs to be more proactive and considers the implications of pesticide exposure for CHA procedures and processes.

Modulatory role of GSTM1 null genotype on the frequency of micronuclei in pesticide-exposed agricultural workers.

In this study, we aimed to investigate the extent of genotoxic risk and the association between null GSTM1/GSTT1 and GSTP1 Ile105Val variants and cellular DNA damage, as measured by micronucleus (MN) assay in a group of agricultural workers from Denizli, Turkey. Peripheral blood samples were collected from 116 subjects, including 58 workers who were occupationally exposed to pesticides and 58 healthy unexposed controls. The MN frequencies of each individual were assessed by cytokinesis-blocked micronuclei assays on lymphocytes. Genotypes for different GST variants were determined using polymerase chain reaction-based methods. A significant 3.4-fold increase in MN frequency was observed in workers compared with the controls (p < 0.001). Among the GST genotypes, only the GSTM1 null genotype was found to be significantly associated with an increased MN frequency in workers (p = 0.01). Individuals with a concomitant null GSTM1/GSTT1 genotype demonstrated a significant (p = 0.01) increase in MN frequency compared with those with functional isozymes in the exposed worker group. The association of the GSTM1 null genotype with higher MN frequency suggests that it may be a modifier of genotoxic risk in individuals exposed to pesticides and may thus be a candidate susceptibility biomarker for human biomonitoring studies.

Vitamin D insufficient levels during pregnancy and micronuclei frequency in peripheral blood T lymphocytes mothers and newborns (Rhea cohort, Crete)

Vitamin D deficiency is common among pregnant women and may be associated with several adverse health outcomes including cancer. Micronuclei frequency is a biomarker of early genetic effects and has been used to examine the association between genotoxic exposures and cancer. We examined maternal vitamin D levels during pregnancy in associations with micronuclei frequency in maternal blood and in cord blood. 173 mothers and 171 newborns born between 2007 and 2008 in Heraklion (Crete, Greece) were included in the study. Between 14th and 18th weeks of gestation we collected information on maternal diet using food frequency questionnaires (FFQs). We measured maternal serum concentrations of 25-hydroxyvitamin D [25(OH)D] between the first and second trimester of pregnancy. We estimated dietary vitamin D intake using information from FFQ. After delivery we collected cord blood and maternal peripheral blood. We used the cytokinesis-block micronucleus (CBMN) assay to assess the frequencies of micronucleated cells in binucleated T lymphocytes (MNBN). Maternal insufficient serum levels of 25(OH)D (<50nmol/L) during pregnancy were associated with increased MNBN frequency in cord blood [IRR=1.32 (95%CI: 1.00, 1.72)]. This increase was higher for newborns with birth weight above the third quartile [≥3.500kg; IRR=2.21 (1.26, 3.89)]. Similarly, low levels of dietary vitamin D were associated with increased MNBN frequency in cord blood [middle tertile IRR=1.08 (0.78, 1.47), lower tertile IRR=1.51 (1.06, 2.14)]. Insufficient levels of vitamin D were not associated with MNBN in mothers. Our results suggest that vitamin D deficiency during pregnancy increases genotoxic risks in newborns. The prevalence of vitamin D deficiency globally is high and it is important to further investigate whether vitamin D supplementation or similar interventions during pregnancy could prevent DNA damage at early stages of life.

Targeting safety in the clinic for precise genome editing using CRISPR: a genotoxicologist's perspective.

Targeting safety in the clinic for precise genome editing using CRISPR: a genotoxicologist's perspective.