Chromosome aberrations, micronucleus frequency, and catalase concentration in a population chronically exposed to high levels of radon.

PURPOSE: To deepen our knowledge on the effects of high levels of indoor radon exposure, we assessed the frequencies of unstable and stable chromosome aberrations and micronucleus (MN), as well as the concentration of an endogenous antioxidant (catalase, CAT), in blood samples of individuals chronically exposed to high indoor radon concentrations in Indonesia (Tande-Tande sub-village, Mamuju, West Sulawesi). Moreover, we also investigated the occurrence of a radio-adaptive response (RAR) in Tande-Tande sub-village inhabitants using the G2 MN assay. MATERIALS AND METHODS: The frequencies of dicentric (DC), acentric (AF), ring (R), and translocation (Tr) chromosomes in Tande-Tande inhabitants were compared to those in people living in a reference area with low levels of indoor radon levels (Topoyo village, Indonesia). The number of MN per 1000 binucleated cells (BNC) and CAT concentration per total protein was quantified and compared between groups. Lastly, we irradiated (2 Gy) phytohemagglutinin-stimulated samples in vitro and measured the frequency of MN to verify the occurrence of a RAR in Tande-Tande sub-village inhabitants. RESULTS AND CONCLUSION: The frequencies of DC, AF, and Tr did not differ between Tande-Tande inhabitants and control subjects (p = 0.350, 0.521, 0.597). The frequency of MN in Tande-Tande inhabitants was significantly lower than that in the control group (p = 0.006). Similarly, CAT concentration in Tande-Tande inhabitants was also significantly lower than that in the control population (p < 0.001). Significant negative correlations were identified for MN number and CAT concentration versus indoor radon concentration, annual effective dose, or cumulative dose both within groups and when all data were analyzed together. Our findings indicate that, despite the high indoor radon levels, Tande-Tande inhabitants are not under oxidative stress, since this group had lower CAT concentration and MN frequency than those in the control group. The negative correlation between MN frequency and indoor radon concentration, annual effective dose, and cumulative dose suggests the occurrence of an RAR phenomenon in Tande-Tande sub-village inhabitants. This interpretation is also supported by the results of the G2 MN assay, which revealed lower MN frequencies after in vitro irradiation of samples from Tande-Tande sub-village inhabitants than those in samples from the control group (p = 0.0069, for cumulative MN frequency; p = 0.0146, for radiation-induced MN only).

Genetic damage in lymphocytes of lung cancer patients is correlated to the composition of the respiratory tract microbiome.

Recent findings indicate that the microbiome may have significant impact on the development of lung cancer by its effects on inflammation, dysbiosis or genome damage. The aim of this study was to compare the sputum microbiome of lung cancer (LC) patients with the chromosomal aberration (CA) and micronuclei (MN) frequency in peripheral blood lymphocytes. In the study, the taxonomic composition of the sputum microbiome of 66 men with untreated LC were compared with 62 control subjects with respect to CA and MN frequency and centromere fluorescence in situ hybridisation analysis. Results showed a significant increase in CA (4.11 ± 2.48% versus 2.08 ± 1.18%) and MN (1.53 ± 0.67% versus 0.87 ± 0.49%) frequencies, respectively, in LC patients as compared to control subjects. The higher frequency of centromeric positive MN of LC patients was mainly due to aneuploidy. A significant increase in Streptococcus, Bacillus, Gemella and Haemophilus in LC patients was detected, in comparison to the control subjects while 18 bacterial genera were significantly reduced, which indicates a decrease in the beta diversity in the microbiome of LC patients. Although, the CA frequency in LC patients is significantly associated with an increased presence of the genera Bacteroides, Lachnoanaerobaculum, Porphyromonas, Mycoplasma and Fusobacterium in their sputum, and a decrease for the genus Granulicatella after application of false discovery rate correction, significance was not any more present. The decrease of MN frequency of LC patients is significantly associated with an increase in Megasphaera genera and Selenomonas bovis. In conclusion, a significant difference in beta diversity of microbiome between LC and control subjects and association between the sputum microbiome composition and genome damage of LC patients was detected, thus supporting previous studies suggesting an etiological connection between the airway microbiome and LC.

Genomic instability in Buccal mucosal cells of children living in abnormal conditions from Santos-Sao Vicente Estuary.

The aim of this study was to evaluate genomic instability and cytotoxicity in buccal mucosa cells of children living in abnormal conditions from Santos Sao Vicente estuary. The study area is located between coordinates 23°58'11.8"S and 46°24'26.3"W, in the southwestern zone of the Sao Paulo State, Brazil. A total of 40 children was distributed into two groups: exposed and non-exposed groups. The frequency of micronuclei increased to buccal mucosa cells of children living in Santos Sao Vicente estuary when compared to the non-exposed group (p < 0.05). No remarkable differences on buccal cells were found inpyknosis, karyorrhexis and karyolysi between groups. Taken together, our results suggest that children living in contaminated areas comprise a high group for genomic instability on buccal mucosa cells. Given that the current investigation is a preliminary study, further analysis with a larger sample of children is interesting as a future perspective.

Risk of genotoxic damage in schoolchildren exposed to organochloride pesticides.

This study identified and determined organochloride pesticide (OCs) concentrations in hair samples from children at two elementary schools: one exposed to fumigations in agricultural fields, the other unexposed. Three concentrations of OCs levels in the hair were compared (high, medium, low), and total nuclear abnormalities in buccal cells were determined: micronuclei (MNi), condensed chromatin, karyorrhexis, pyknosis, binucleate cells, karyolysis, lobed nuclei, and apoptosis. No significant differences were found for the presence of MNi between the schoolchildren from the exposed and unexposed schools, but the prevalence of OCs in both schools was over 50%, as well as the frequencies of MNi in the children were over 58%. Findings show a significant difference between the frequency of MNi in the total sample of schoolchildren (exposed school + unexposed school) in relation to the concentration of OCs detected in their hair. The children from exposed school that showed the higher concentrations of OCs in hair had higher levels of genotoxic damage in the buccal cells; compared against children with lower concentrations of OCs. The most frequent nuclear abnormalities in the exposed children were lobed nuclei (79.4%), binucleate cells (66.66%), apoptosis (65.07), and MNi (58.7%). We determined the prevalence ratio (PR) and prevalence odds ratio (POR) for the presence of MNi in buccal cells in relation to the OCs concentrations in the hair samples. Both ratios were high for MNi [PR 3.93, 95% confidence interval (CI) 1.97-7.84, p = 0.0003; and POR 7.97, 95% CI 2.62-24.28, p = 0.0003], indicating a 7.97 times greater risk that the exposed children will present > 0.2% of MNi when OCs concentrations exceed 0.447 µg/g. These indicators may be useful biomarkers of genotoxic damage in children exposed to persistent, highly-toxic compounds. Results suggest the potential risk to which those schoolchildren are exposed on a daily basis due to fumigations in nearby agricultural fields.

Buccal micronucleus cytome assay: Inter-laboratory scoring exercise and micronucleus and nuclear abnormalities frequencies in different populations from Brazil.

The Buccal Micronucleus Cytome Assay (BMCyt) has become an important biomonitoring tool for assessing cytogenetic damage in many studied populations. Each laboratory applies protocols that vary according to the method of collecting and preparing samples. Besides, Brazil is a country of great territorial extensions that received immigrants from various parts of the world with different genetic backgrounds. Therefore, the present study aimed to evaluate the inter-laboratory variation in scoring the same set of slides using the more comprehensive scoring criteria, to standardize the BMCyt protocol, to observe the basal alterations in populations of different Brazilian regions and to compare it with other places around the world. Our results showed that a valuable number of laboratories participated, ten laboratories from different regions of the country, for the validation of the BMCyt in human biomonitoring studies, resulting in the 804 healthy individuals. This was possible because we observed: a range of measures needs to be considered, such as the baseline frequency of DNA damage and cell death in non-exposed individuals; age when grouped showed an influence on DNA damage, although when evaluated by group we did not see an influence; association between smoking habit and all endpoints of the BMCyt (except karyolytic cells) was evident; the basal MN frequency, in the majority of groups, follows those around the world; and the BMCyt was confirmed as a good health status biomarker. We emphasize the need for constant discussions on the parameters of cell death due to greater difficulty among the analyzers.

Analysis of historical negative control group data from the rat in vivo micronucleus assay.

A database of micronuclei counts for historical negative control data from rat in vivo micronuclei tests performed in 10 different laboratories was established. Data were available from over 4000 negative control rats from 10 laboratories. The mean frequency of micronucleated cells (MN)/1000 cells ranged from 0.44 to 2.22, a 5-fold range. Overall there were no major sex or strain differences in frequency, although there were some small but statistically significant differences within laboratories. There was appreciable variability between experiments compared with variability within experiments in some laboratories. No specific factor was identified which could explain this variability although it was noted that many different vehicles were used in the experiments. It is hoped that these data will help laboratories beginning studies with the rat micronucleus assay and those involved in the assessment of micronucleus assay results.

Serum albumin adducts, DNA adducts and micronuclei frequency measured in benzo[a]pyrene-exposed mice for estimation of genotoxic potency.

The environmental and food contaminant, benzo[a]pyrene {B[a]P, a polycyclic aromatic hydrocarbon (PAH)}, is classified as a human carcinogen by the International Agency for Research on Cancer. The carcinogenicity of B[a]P is linked to the formation of electrophilic metabolites, namely B[a]P-diol epoxides (BPDEs) occurring as stereoisomers. In this work, we quantified the metabolic formation of BPDE isomers and the genotoxic effect in B[a]P-exposed mice, with an aim to estimate the genotoxic potency of B[a]P per in vivo dose of its most potent metabolite [i.e. (+)-anti-BPDE]. The increase in frequency of micronuclei (fMN) in erythrocytes was measured as a biomarker for genotoxic effect. Covalent adducts to serum albumin (SA) and those to DNA from the BPDEs were analysed using liquid chromatography tandem mass spectrometry (LC-MS/MS), as adducts to histidine (BPDE-His-Pro) and deoxyguanosine (BPDE-dG), respectively. For the first time in animal experiments it was possible to resolve adducts to SA from (+)-anti-, (-)-anti- and (±)-syn-BPDE isomers by LC-MS/MS. The adduct levels in the protein were about 16 fmol/mg SA, which was orders of magnitude lower than that in the nucleic acid, 28 pmol/mg DNA, in mice exposed to 100 mg B[a]P per kg body weight (bw). Using SA adduct levels, the in vivo dose of (+)-anti-BPDE was calculated to be approximately 50 nM·h per mg B[a]P per kg bw. This allowed to make a preliminary estimate of the genotoxic potency as 2‰ fMN per µM·h of (+)-anti-BPDE. This estimate was compared to that from another food toxicant, glycidol, studied with similar methods, which indicated that the BPDE has several orders of magnitude higher genotoxic potency. The demonstrated approach on integrating biomarkers of internal dose of a causative agent and that of genotoxic effect for assessing genotoxic potency, using B[a]P as a model, has a potential for improving cancer risk assessment procedures for PAHs.

Micronuclei frequency in peripheral blood lymphocytes of healthy subjects living in turin (North-Italy): contribution of body mass index, age and sex.

Background: Increased micronuclei (MNi) frequencies in human lymphocytes are an indicator of chromosome instability and could be influenced by different exogenous and endogenous factors. The increased exposure to environmental pollutants has led to the awareness of the necessity for constant monitoring of urban human populations.Aim: We evaluated the MNi frequency in a sample belonging to the non-occupationally exposed population of Turin (North-Western Italy). A possible effect of body mass index, age and sex on the genomic damage levels was also investigated.Subjects and Methods: The study included 150 subjects. MNi, nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) were scored in 1,000 lymphocytes per subject.Results: The MNi, NPBs and NBUDs average frequencies (‰ ± S.D.) were 7.19 ± 2.51, 1.65 ± 1.54 and 2.07 ± 1.76, respectively. Turin shows one of the highest MNi frequencies with respect to other Italian cities and European regions. A significant correlation was found between MNi, NPBs, NBUDs frequencies, age and body mass index.Conclusion: Baseline MNi frequency was established in a sample of a city, like Turin, exposed to high levels of environmental pollutants. We hope that the results of this study can be used as a stimulus for future biomonitoring programmes in other Italian and globally distributed cities.

Genotoxic effects of tobacco use in residents of hilly areas and foot hills of Western Ghats, Southern India.

Smoking and smokeless tobacco consumption is a significant risk factor that provokes genetic alterations. The present investigation was to evaluate the biomarkers of genotoxicity including micronucleus (MN), chromosome aberrations (CA) and DNA strand breaks among tobacco consumers and control individuals residing in hilly areas of Western Ghats, Tamilnadu, South India. This study included 268 tobacco consumers with equal number of controls. The tobacco consumers were divided into Group I (<10 years of tobacco consumption with an age range from 15 to 35 years) and group II (>10 years consumption above 35 years of age). Chromosome aberration (CA) and comet assay were performed using blood and micronucleus assay from exfoliated buccal epithelial cells obtained from tobacco consumers and controls. Elevated levels of CA were found in group II (Chromatid type: 2.39 ± 1.13 and chromosome type: 1.44 ± 1.24) exposed subjects, high micronucleus and DNA damage (TL:4.48 ± 1.24 and TM:3.40 ± 1.58) levels were significantly (p < 0.05) observed in both smoking and smokeless tobacco consumers when comparison with group I and controls. This study also observed a lack of awareness among the tobacco consumers about the harmful health effects of tobacco. Tobacco consumption contributes to the significant alteration in genetic materials. In addition, a high rate of spontaneous abortion was also seen in the studied population.

Increased genomic damage and vitamin B status in inflammatory bowel disease patients: A case-control, prospective, pilot study.

Vitamin B deficiency in patients with inflammatory bowel disease (IBD) is well-documented; however, few studies have explored genomic damage in patients with IBD using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. This study investigated the frequency of micronuclei (MNi) using the CBMN-Cyt assay and the level of vitamin B in patients with IBD. This prospective study was conducted in 15 patients with ulcerative colitis, 15 patients with Crohn's disease, and 30 healthy controls from one tertiary hospital. Serum vitamin B and homocysteine levels were measured, and the MNi status was analyzed using the CBMN-Cyt assay. The patients with IBD showed significantly lower serum pyridoxine levels and significantly higher homocysteine levels than controls. The frequencies of binucleated cells (BNCs) with MNi, nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) were 8.5 [5.8-13.5], 1.0 [0.0-1.9], and 5.4 [4.3-7.4] for the IBD group, and 5.9 [4.8-7.7], 0.2 [0.0-1.0], and 3.5 [2.9-5.4] for the control group (P = 0.011, P = 0.010, and P = 0.002), respectively. This study suggests that patients with IBD have increased frequencies of MNi and decreased levels of pyridoxine than healthy controls.

Multiple metals exposure and chromosome damage: Exploring the mediation effects of microRNAs and their potentials in lung carcinogenesis.

OBJECTIVE: This study aimed to investigate the associations of multiple metals with chromosome damage, and further explore the mediation roles of microRNAs (miRNAs) and their potentials in lung cancer. METHODS: We determined the urinary levels of 23 metals, lymphocytic micronucleus (MN) frequency, and ten candidate miRNAs in plasma among 365 healthy workers. Poisson and linear regression models were conducted to analyze the associations of urinary metals with MN frequency and miRNAs, respectively. The mediation effects of miRNAs on the metal-MN frequency associations were assessed by causal mediation analysis. Additionally, the levels of effective metal and miRNAs were measured in 43 pair-wised tumor and normal lung tissues. RESULTS: The urinary level of titanium was inversely associated with MN frequency after Bonferroni correction [frequency ratio (FR) and 95% confidence interval (95%CI) = 0.88 (0.82, 0.94), p = 5.0 × 10-4]. A doubling in urinary titanium was associated with 14.72%-38.17% decrease in plasma miRNAs. After multiple comparison, miR-24-3p and miR-28-5p significantly mediated 24.8% (7.7%, 70.0%) and 20.4% (5.7%, 52.0%) of the association between titanium and MN frequency (pmediation = 0.002 and 0.004, respectively). Besides, a doubling in titanium was associated with a separate 53.4% and 47.2% decreased miR-24-3p and miR-28-5p expression in normal lung tissues. Lower titanium but higher levels of miR-24-3p and miR-28-5p were shown in tumor than normal tissues of lung squamous cell carcinoma patients (all p < 0.05). CONCLUSIONS: Our study proposed the negative associations of titanium with chromosome damage and lung cancer, and highlighted the mediating roles of miR-24-3p and miR-28-5p. Further investigations are warranted to validate these associations and uncover the underlying mechanisms.

Maternal diet during pregnancy and micronuclei frequency in peripheral blood T lymphocytes in mothers and newborns (Rhea cohort, Crete).

PURPOSE: The study assessed whether diet and adherence to cancer prevention guidelines during pregnancy were associated with micronucleus (MN) frequency in mothers and newborns. MN is biomarkers of early genetic effects that have been associated with cancer risk in adults. METHODS: A total of 188 mothers and 200 newborns from the Rhea cohort (Greece) were included in the study. At early-mid pregnancy, we conducted personal interviews and a validated food frequency questionnaire was completed. With this information, we constructed a score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines on diet, physical activity and body fatness. At delivery, maternal and/or cord blood was collected to measure DNA and hemoglobin adducts of dietary origin and frequencies of MN in binucleated and mononucleated T lymphocytes (MNBN and MNMONO). RESULTS: In mothers, higher levels of red meat consumption were associated with increased MNBN frequency [2nd tertile IRR = 1.34 (1.00, 1.80), 3rd tertile IRR = 1.33 (0.96, 1.85)] and MNMONO frequency [2nd tertile IRR = 1.53 (0.84, 2.77), 3rd tertile IRR = 2.69 (1.44, 5.05)]. The opposite trend was observed for MNBN in newborns [2nd tertile IRR = 0.64 (0.44, 0.94), 3rd tertile IRR = 0.68 (0.46, 1.01)], and no association was observed with MNMONO. Increased MN frequency in pregnant women with high red meat consumption is consistent with previous knowledge. CONCLUSIONS: Our results also suggest exposure to genotoxics during pregnancy might affect differently mothers and newborns. The predictive value of MN as biomarker for childhood cancer, rather than adulthood, remains unclear. With few exceptions, the association between maternal carcinogenic exposures during pregnancy and childhood cancer or early biologic effect biomarkers remains poorly understood.

Genetic damage in Rhinella marina populations in habitats affected by agriculture in the middle region of the Sinú River, Colombia.

Contamination with pesticide residues affects the environmental health of agroecosystems, especially the amphibian fauna that lives in these environments. The objective of the present study was to determine pesticides concentrations in sediments of agroecosystems and to evaluate genetic damage in Rhinella marina populations living in these zones. A total of 91 individuals were collected, 51 in the group exposed in different areas of the middle region of the Sinú River (Irrigation District of Mocari 16, Irrigation District of Aguas Negras 21, Irrigation District of Cerete 14) and 40 in a control group; at the same time, 36 subsamples of sediments were taken at each sampled station to determine pesticides organochlorine by means of chromatography coupled with ISQ Thermo Scientific mass spectrometer. The micronucleus test was applied in erythrocytes of the individuals collected. Results showed the presence of persistent organochlorine pesticides (POPs) in the sediment samples (p,p'-DDT, p,p'-DDE, and p,p'-DDD) of agricultural soils. Two individuals were registered with abnormalities in their limbs at the Mocari station, representing 12.5% of the morphological malformations to this sector. Micronucleus analysis revealed statistically significant genetic damage in exposed individuals (Mocari 9.87 ± 5.1, Cerete 7.7 ± 1.7, Aguas Negras 5.6 ± 3.6) with respect to the control group (2.4 ± 1.9) (p < 0.05). Spearman correlation analysis revealed a positive association between genetic damage and POP concentrations (p < 0.05). In addition, cellular alterations such as nuclear buds, and pyknosis (cell death), were statistically significant in the exposed group compared to the control group (p < 0.05). This study suggests that there is evidence for morphological and genotoxic effects in R. marina populations inhabiting areas influenced by agriculture, possibly associated with the presence of p,p'-DDT, p,p'-DDD, and p,p'-DDE.

Sensitivity and specificity prediction of the buccal micronucleus cytome assay in end-stage renal disease patients on dialysis: A case-control study.

Patients with end-stage renal disease (ESRD) require hemodialysis. However, dialysis therapy may cause genomic damage due to increased oxidative stress. Non-invasive assessment of genotoxicity may be helpful for developing management strategies. We applied the buccal micronucleus cytome (BMCyt) assay to ESRD patients on dialysis. Patients (n=35, age 52±2 year) on dialysis therapy (20.9±0.8months) had low glomerular filtration rates (GFR=5.00±0.36ml/min/1.73m2); controls (n=21, age 51±2 year) were healthy adults with no known recent illnesses or exposures. Patients had significantly increased chromosome damage: clastogenic/aneugenic events (frequency of cells with MN), cellproliferation (basal cells), cytokinesis defects (binucleated cells), and celldeath (pyknotic cells); Repair Index was lower in the patient group. Receiver Operator Characteristic (ROC) curve analysis showed that cells with MN were the best predictor for discriminating between patients and controls. Other predictivebiomarkers were the frequencies of basal, binucleated,and pyknotic.

Is mobile phone radiation genotoxic? An analysis of micronucleus frequency in exfoliated buccal cells.

Electromagnetic fields (EMF) are classified as "possibly carcinogenic" by the International Agency for Research on Cancer (IARC). Some publications have reported associations between EMF exposure and DNA damage, but many other studies contradict such findings. Cytomorphological changes, such as micronuclei (MN), indicative of genomic damage, are biomarkers of genotoxicity. To test whether mobile phone-associated EMF exposure affects the MN frequency in exfoliated buccal cells, we obtained cells smears from the left and right inner cheeks of healthy mobile phone users, aged 18-30 (n=86), who also completed a characterization survey. MN frequencies were tested for potential confounding factors and for duration of phone use and preferential side of mobile phone use. No relationship was observed between MN frequency and duration of mobile phone use in daily calls. Cells ipsilateral to mobile phone use did not present a statistically significantly higher MN frequency, compared to cells contralateral to exposure. A highly statistically significant (p<0.0001) increase in MN frequency was found in subjects reporting regular exposure to genotoxic agents. Therefore, our results suggest that mobile phone-associated EMF do not to induce MN formation in buccal cells at the observed exposure levels.

Analysis of microRNA expression and micronuclei frequency in workers exposed to vinyl chloride monomer in China.

AIM: To identify differently expressed miRNAs associated with vinyl chloride monomer (VCM) and micronuclei (MN) frequency. METHOD: In discovery stage, we used microarray to detect miRNAs expression in peripheral blood lymphocytes between six low and six high VCM-exposed workers grouped by medium cumulative exposure dose. Then we validated four miRNAs using real-time quantitative reverse transcription PCR (qRT-PCR) and detected the micronuclei frequencies using cytokinesis-block micronucleus assay in 94 VCM-exposed workers and 53 healthy control subjects. RESULTS & CONCLUSION: We found eight miRNAs significantly downregulated and seven miRNAs upregulated (|Fold Change| >2; p < 0.05) in the high-exposure group through microarray. We validate that miR-222-3p, miR-146a-5p and miR-151a-5p were downregulated, while miR-22-3p was upregulated in VCM-exposed group (all p < 0.01). Furthermore, we found that expression of miR-22-3p was upregulated in the high micronuclei (MN) frequency subjects. In conclusion, our study suggested that these four miRNAs could be biomarkers of VCM exposure, and moreover miR-22-3p was correlated with MN frequency.

Frequencies of micronucleated reticulocytes, a dosimeter of DNA double-strand breaks, in infants receiving computed tomography or cardiac catheterization.

The use of computed tomography (CT scans) has increased dramatically in recent decades, raising questions about the long-term safety of CT-emitted x-rays especially in infants who are more sensitive to radiation-induced effects. Cancer risk estimates for CT scans typically are extrapolated from models; therefore, new approaches measuring actual DNA damage are needed for improved estimations. Hence, changes in a dosimeter of DNA double-strand breaks, micronucleated reticulocytes (MN-RETs) measured by flow cytometry, were investigated in mice and infants exposed to CT scans. In male C57BL/6N mice (6-8 weeks-of-age), there was a dose-related increase in MN-RETs in blood samples collected 48h after CT scans delivering targeted exposures of 1-130 cGy x-rays (n=5-10/group, r=0.994, p=0.01), with significant increases occurring at exposure levels as low as 0.83 cGy x-rays compared to control mice (p=0.002). In paired blood specimens from infants with no history of a prior CT scan, there was no difference in MN-RET frequencies found 2h before (mean, 0.10±0.07%) versus 48h after (mean, 0.11±0.05%) a scheduled CT scan/cardiac catheterization. However, in infants having prior CT scan(s), MN-RET frequencies measured at 48h after a scheduled CT scan (mean=0.22±0.12%) were significantly higher than paired baseline values (mean, 0.17±0.07%; p=0.032). Increases in baseline (r=0.722, p<0.001) and 48-h post exposure (r=0.682, p<0.001) levels of MN-RETs in infants with a history of prior CT scans were significantly correlated with the number of previous CT scans. These preliminary findings suggest that prior CT scans increase the cellular responses to subsequent CT exposures. Thus, further investigation is needed to characterize the potential cancer risk from single versus repeated CT scans or cardiac catheterizations in infants.

Genotoxic and mutagenic effects of passive smoking and urban air pollutants in buccal mucosa cells of children enrolled in public school.

Nuclear abnormalities (micronuclei and meta-nuclear changes) have been used as biomarkers to identify cell damages. As children are more vulnerable to the adverse effects of pollution when compared to adults, assessing genetic damage caused by environmental influences is of great interest. As such, the objective was to determine metanuclear (karyolysis, pycnosis, karyorrhexis, binucleated cells, chromosome bridges and micronuclei) in cells from the oral mucosa of children associated with the school environment, gender, exposure to cigarette smoke and vehicular traffic. Analyses of nuclear abnormalities were performed in exfoliated buccal cells of children from two public schools located in Dourados - MS. The data were analyzed through Kruskal-Wallis test considering a significance level of 5% (p < .05). The results showed that children exposed to cigarette smoke presented higher levels of nuclear abnormalities than children who were not usually exposed to this type of mutagenic and genotoxic agent, suggesting that such contaminants are related to clastogenic and aneugenic effects on DNA. Moreover, female children had higher amounts of nuclear abnormalities when compared to male children. With regards to the school environment, the study results indicated statistical differences in of term chromosomal abnormalities for schools A and B. Thus, it was possible to determine that children exposed to cigarette smoke are susceptible to further genetic damage than unexposed children, and female children may be more susceptible to genotoxic and mutagenic agents. This study contributes to the current knowledge on the mutagenic characteristics of human cells, supporting the adoption of preventive Public Health measures.

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.