A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements.

Chromosomal instability (CIN) generates micronuclei-aberrant extranuclear structures that catalyze the acquisition of complex chromosomal rearrangements present in cancer. Micronuclei are characterized by persistent DNA damage and catastrophic nuclear envelope collapse, which exposes DNA to the cytoplasm. We found that the autophagic receptor p62/SQSTM1 modulates micronuclear stability, influencing chromosome fragmentation and rearrangements. Mechanistically, proximity of micronuclei to mitochondria led to oxidation-driven homo-oligomerization of p62, limiting endosomal sorting complex required for transport (ESCRT)-dependent micronuclear envelope repair by triggering autophagic degradation. We also found that p62 levels correlate with increased chromothripsis across human cancer cell lines and with increased CIN in colorectal tumors. Thus, p62 acts as a regulator of micronuclei and may serve as a prognostic marker for tumors with high CIN.

Micronuclear collapse from oxidative damage.

Chromosome-containing micronuclei are a hallmark of aggressive cancers. Micronuclei frequently undergo irreversible collapse, exposing their enclosed chromatin to the cytosol. Micronuclear rupture catalyzes chromosomal rearrangements, epigenetic abnormalities, and inflammation, yet mechanisms safeguarding micronuclear integrity are poorly understood. In this study, we found that mitochondria-derived reactive oxygen species (ROS) disrupt micronuclei by promoting a noncanonical function of charged multivesicular body protein 7 (CHMP7), a scaffolding protein for the membrane repair complex known as endosomal sorting complex required for transport III (ESCRT-III). ROS retained CHMP7 in micronuclei while disrupting its interaction with other ESCRT-III components. ROS-induced cysteine oxidation stimulated CHMP7 oligomerization and binding to the nuclear membrane protein LEMD2, disrupting micronuclear envelopes. Furthermore, this ROS-CHMP7 pathological axis engendered chromosome shattering known to result from micronuclear rupture. It also mediated micronuclear disintegrity under hypoxic conditions, linking tumor hypoxia with downstream processes driving cancer progression.

Genotoxicity and Micronucleus Formation as a Result of Panoramic Radiography in Epithelial Cells of the Buccal Mucosa: A Cross-sectional Study in Adults.

OBJECTIVES: To determine the genetic effects of panoramic radiography on the epithelial cells of the buccal mucosa by examining the micronucleus formation in these cells. MATERIALS AND METHODS: In this cross-sectional study, exfoliative cytology samples were prepared from the buccal mucosa of 36 patients immediately before and 10 days after panoramic radiography. The samples were prepared using liquid-based cytology with Papanicolaou staining. The slides were simultaneously evaluated by two expert pathologists and the ratio of the number of cells with micronuclei to the total number of cells on the slide was reported as a percentage. Data analysis was done using paired-samples T test, Pearson's correlation coefficient, and covariance analysis (α = 0.05). RESULTS: The study sample consisted of 24 (66.67%) males and 12 females (33.33%) with a mean (SD) age of 27.36 (8.19) years. The frequency of cells with micronucleus before and after panoramic radiography was not statistically different (p = 0.468). Additionally, the frequency of micronucleated cells was not correlated with age (p = 0.737) and sex (p = 0.211). CONCLUSION: Panoramic exposure slightly increased the frequency of cells with micronucleus in epithelial cells of the buccal mucosa. However, this increase was not statistically significant.

Genotoxicity of selected cannabinoids in human lymphoblastoid TK6 cells.

Natural non-psychoactive cannabinoids such as cannabigerol (CBG), cannabidiol (CBD), cannabichromene (CBC), cannabidivarin (CBDV), and cannabinol (CBN) are increasingly consumed as constituents of dietary products because of the health benefits claims. Cannabinoids may reduce certain types of pain, nausea, and anxiety. Anti-inflammatory and even anti-carcinogenic properties have been discussed. However, there are insufficient data available regarding their potential (geno-)toxic effects. Therefore, we tested CBG, CBD, CBC, CBDV, and CBN for their genotoxic potential and effects on mitosis and cell cycle in human lymphoblastoid TK6 cells. The selected cannabinoids (except CBDV) induced increased micronuclei formation, which was reduced with the addition of a metabolic activation system (S9 mix). CBDV induced micronuclei only after metabolic activation. Mitotic disturbances were observed with all tested cannabinoids, while G1 phase accumulation of cells was observed for CBG, CBD and CBDV. The genotoxic effects occurred at about 1000-fold higher concentrations than are reported as blood levels from human consumption. However, the results clearly indicate a need for further research into the genotoxic effects of cannabinoids. The mechanism of the mitotic disturbance, the shape of the dose-response curves and the possible effects of mixtures of cannabinoids are aspects which need clarification.

Di(2-ethylexyl) phthalate and chromosomal damage: Insight on aneugenicity from the cytochalasin-block micronucleus assay.

Bis(2-ethylhexyl) phthalate is the most abundant phthalate used as plasticizer to soften plastics and polymers included in medical devices. Human and environmental exposure may occur because DEHP is not chemically bound to plastics and can easily leach out of the materials. This phthalate is classified as reproductive toxicant and possible carcinogen to humans. The genotoxic potential has still to be clarified, but there are indications suggesting that DEHP may have aneugenic effects. To further investigate DEHP genotoxicity, the cytochalasin-block micronucleus assay was applied and combined with the CREST staining to characterise micronucleus content and gain insights on its genotoxic mode of action. Chromosomal damage was also analysed in metaphase and ana-telophase cells and the morphology of the mitotic spindle was investigated to evaluate the possible involvement of this cellular apparatus as a target of DEHP. Our findings indicated that DEHP induced a statistically significant increase in the frequency of micronuclei as well as in the frequency of CREST-positive micronuclei. Consistently, disturbance of chromosome segregation and induction of numerical chromosome changes were observed together with changes in spindle morphology, formation of multipolar spindles and alteration of the microtubule network. Experiments performed without metabolic activation demonstrated a direct action of DEHP on chromosome segregation not mediated by its metabolites. In conclusion, there is consistent evidence for an aneugenic activity of DEHP. A thresholded genotoxic activity was identified for DEHP, disclosing possible implications for risk assessment.

Influence of genetic polymorphisms of Hg metabolism and DNA repair on the frequencies of micronuclei, nucleoplasmic bridges, and nuclear buds in communities living in gold mining areas.

Fishing communities living near gold mining areas are at increased risk of mercury (Hg) exposure via bioaccumulation of methylmercury (MeHg) in fish. This exposure has been linked to health effects that may be triggered by genotoxic events. Genetic polymorphisms play a role in the risk associated with Hg exposure. This study evaluated the effect of single nucleotide polymorphisms (SNPs) in metabolic and DNA repair genes on genetic instability and total hair Hg (T-Hg) levels in 78 individuals from "La Mojana" in northern Colombia and 34 individuals from a reference area. Genetic instability was assessed by the frequency of micronuclei (MNBN), nuclear buds (NBUDS), and nucleoplasmic bridges (NPB). We used a Poisson regression to assess the influence of SNPs on T-Hg levels and genetic instability, and a Bayesian regression to examine the interaction between Hg detoxification and DNA repair. Among exposed individuals, carriers of XRCC1Arg399Gln had a significantly higher frequency of MNBN. Conversely, the XRCC1Arg194Trp and OGG1Ser326Cys polymorphisms were associated with lower frequencies of MNBN. XRCC1Arg399Gln, XRCC1Arg280His, and GSTM1Null carriers showed lower NPB frequencies. Our results also indicated that individuals with the GSTM1Nulland GSTT1null polymorphisms had a 1.6-fold risk for higher T-Hg levels. The Bayesian model showed increased MNBN frequencies in carriers of the GSTM1Null polymorphism in combination with XRCC1Arg399Gln and increased NBUDS frequencies in the GSTM1Null carriers with the XRCC3Thr241Met and OGG1Ser326Cys alleles. The GSTM1+ variant was found to be a protective factor in individuals carrying OGG1Ser326Cys (MNBN) and XRCC1Arg280His (NPB); the GSTT1+ polymorphism combined with XRCCArg194Trp also modulated lower MNBN frequencies, while GSTT1+ carriers with the XRCC1Arg399Gln allele showed lower NPB frequencies. Consistent with GSTM1, GSTT1Null carriers with XRCC3Thr241Met showed increased NBUDS frequency. With the rise of gold mining activities, these approaches are vital to identify and safeguard populations vulnerable to Hg's toxic effects.

Frequencies of micronuclei in buccal cells and their spatial distribution in a population living in proximity to coal mining areas in southern Brazil.

The extraction and burning of coal release genotoxic pollutants, and understanding the relationship between genetic damage and the spatial distribution of residences in coal-using regions is crucial. The study aimed to conduct a spatial analysis of genotoxic damage through the of micronuclei (MNs) number and their proximity to coal mining/burning in the largest coal exploration region in Brazil. In this study, the detection of genotoxic damage was performed using the MN assay in oral cells of residents exposed to coal mining activities. Spatial analysis was conducted using QGIS 3.28.10 based on information obtained from a questionnaire administered to the population. Multiple linear regression analysis was carried out to assess the influence of the distance from residential areas to polluting sources on the number of MNs found. Additionally, Spearman's correlation was performed to identify the strength and direction of the association between the frequency of MNs and each of the polluting sources. A total of 147 MNs were quantified among all participants in the coal mining region. Notably, residents living within 2 km and 10 km of pollution sources exhibited the highest prevalence of MNs. The analysis demonstrated a significant correlation between closer proximity to pollution sources and increased MN frequency, underscoring the spatial relationship between these sources and genotoxic damage. Environmental pollutants from anthropogenic sources present a major health risk, potentially leading to irreversible damage. The spatial analysis in this study highlights the importance of targeted public policies. These policies should aim for a sustainable balance between economic development and public health, promoting effective measures to mitigate environmental impacts and protect community health.

Micronuclei as an indicator of genotoxic change in epithelial cells of buccal mucosa after panoramic radiographs.

BACKGROUND: The radiation released at the time of dental panoramic radiographs causes genotoxic and cytotoxic effects on epithelial cells. OBJECTIVE: This research aimed to evaluate the changes in the frequencies of micronucleated cells in patients' buccal epithelial cells following dental panoramic radiography. METHODS: 74 patients were recruited for the study who were advised for panoramic radiographs. Using a wooden spatula, the buccal epithelial cells were scraped from both cheeks before to panoramic radiation exposure and ten days after the panoramic radiation exposure. Giemsa stain was used to stain the cells, and 500 cells were scored on a slide to determine the frequency of micronuclei. To determine the difference between the frequency of micronuclei before and after radiation exposure, a paired t-test was used in the statistical analysis. RESULTS: The proportion of micronuclei cells was 0.11% before radiation exposure and 0.57% following radiation exposure after 10 days. A statistically significant increase in the frequencies of micronuclei was noted after radiation exposure values. CONCLUSION: This study revealed the genotoxicity of epithelial cells with dental panoramic radiation exposure. It is advised to reduce the use of such radiographs and to use only when there is no other diagnostic tool that is helpful or when absolutely essential.

Non-homologous end joining shapes the genomic rearrangement landscape of chromothripsis from mitotic errors.

Mitotic errors generate micronuclei entrapping mis-segregated chromosomes, which are susceptible to catastrophic fragmentation through chromothripsis. The reassembly of fragmented chromosomes by error-prone DNA double-strand break (DSB) repair generates diverse genomic rearrangements associated with human diseases. How specific repair pathways recognize and process these lesions remains poorly understood. Here we use CRISPR/Cas9 to systematically inactivate distinct DSB repair pathways and interrogate the rearrangement landscape of fragmented chromosomes. Deletion of canonical non-homologous end joining (NHEJ) components substantially reduces complex rearrangements and shifts the rearrangement landscape toward simple alterations without the characteristic patterns of chromothripsis. Following reincorporation into the nucleus, fragmented chromosomes localize within sub-nuclear micronuclei bodies (MN bodies) and undergo ligation by NHEJ within a single cell cycle. In the absence of NHEJ, chromosome fragments are rarely engaged by alternative end-joining or recombination-based mechanisms, resulting in delayed repair kinetics, persistent 53BP1-labeled MN bodies, and cell cycle arrest. Thus, we provide evidence supporting NHEJ as the exclusive DSB repair pathway generating complex rearrangements from mitotic errors.

Study of Radiosensitivity and Induction of Radiation Adaptive Response in Peripheral Blood Lymphocytes of Patients with Oncological Diseases Using the Micronuclear Test.

Radiosensitivity to low and medium doses of X-ray radiation and the ability to induce a radiation adaptive response (RAR) of lymphocytes during in vitro irradiation of peripheral blood of patients with cancer were studied. The criterion for cytogenetic damage was the frequency of micronuclei (MN) in cytochalasin-blocked binucleate lymphocytes in culture. It was found that the spontaneous level of cytogenetic damage in the lymphocytes of patients was 2.6 times higher than in healthy volunteers, and there was also significant interindividual variability in values compared to the control cohort. There were no differences in mean values for radiosensitivity to low and medium doses of X-ray between the study groups. There was no correlation between the spontaneous level of MN in lymphocytes and the radiosensitivity of individuals in both groups. RAR was induced with the same frequency and to the same extent in lymphocytes from both patients and healthy individuals.

Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei.

Genome instability is a hallmark of cancer crucial for tumor heterogeneity and is often a result of defects in cell division and DNA damage repair. Tumors tolerate genomic instability, but the accumulation of genetic aberrations is regulated to avoid catastrophic chromosomal alterations and cell death. In ovarian cancer tumors, claudin-4 is frequently upregulated and closely associated with genome instability and worse patient outcomes. However, its biological association with regulating genomic instability is poorly understood. Here, we used CRISPR interference and a claudin mimic peptide to modulate the claudin-4 expression and its function in vitro and in vivo. We found that claudin-4 promotes a tolerance mechanism for genomic instability through micronuclei generation in tumor cells. Disruption of claudin-4 increased autophagy and was associated with the engulfment of cytoplasm-localized DNA. Mechanistically, we observed that claudin-4 establishes a biological axis with the amino acid transporters SLC1A5 and LAT1, which regulate autophagy upstream of mTOR. Furthermore, the claudin-4/SLC1A5/LAT1 axis was linked to the transport of amino acids across the plasma membrane as one of the potential cellular processes that significantly decreased survival in ovarian cancer patients. Together, our results show that the upregulation of claudin-4 contributes to increasing the threshold of tolerance for genomic instability in ovarian tumor cells by limiting its accumulation through autophagy. SIGNIFICANCE: Autophagy regulation via claudin-4/SLC1A5/LAT1 has the potential to be a targetable mechanism to interfere with genomic instability in ovarian tumor cells.

Genotoxicity of Gamma Radiation Against Lymphocytes of Radiation Workers: The Cytokinesis-Block Micronucleus Assay.

<b>Background and Objective:</b> Gamma irradiation induces genotoxicity, characterized by the formation of extra-nuclear bodies and left behind during the anaphase stage of cell division, often referred to as a micronucleus (MN). The present work aims to monitor exposure to ionizing radiation as a genotoxic agent in the lymphocytes of workers at radiation energy centers. <b>Materials and Methods:</b> The lymphocyte cytokinesis block micronucleus assay used and analyzed the correlation between the Nuclear Division Index (NDI), age, blood type and the number of micronuclei (MN). Blood samples were collected from 20 volunteers in heparin tubes, exposed to 2 Gy gamma rays and cultured <i>in vitro</i>. <b>Results:</b> A significant difference in the number of micronuclei between blood group A and blood groups A, B and AB. The Nuclear Division Index (NDI) value for lymphocytes of radiation energy center workers after gamma radiation was significant (1.74±0.1) but still within the normal range. Neither MN frequency nor NDI values correlated with age, but MN frequency showed a correlation with blood type. <b>Conclusion:</b> The gamma irradiation did not induce a cytostatic effect but proved genotoxic to the lymphocytes of radiation energy center workers. Notably, blood type A demonstrated higher sensitivity to gamma radiation.

Presence of micronuclei and nuclear abnormalities in Caracara (Polyborus) plancus living in an airport area in southern Brazil.

The aviation sector is believed to be responsible for considerable environmental damage attributed to emission of a large number and amount of pollutants. Airports are often surrounded by forest fragments and humid areas that attract birds of prey and hence may potentially serve as useful bioindicators. The aim of the present study was to examine genotoxic potential in raptors exposed to airport pollution using the micronucleus (MN) test and morphological changes as evidenced by bilateral symmetry. This investigation was conducted at Salgado Filho International Airport of Porto Alegre - RS as well as in private and zoological breeding grounds. The presence of metals was measured in the blood cells of the collected birds. Seventeen birds (Caracara (Polyborus) plancus) were used in this study 11 from exposed and 6 from non-exposed group. The nuclear alterations clearly indicate that organisms exposed to airport pollution exhibited a significantly higher frequency of genetic damage compared to non-exposed birds. Further, manganese and chromium were detected exclusively in the blood of the exposed group. In contrast, the analysis of bilateral symmetry did not detect any significant morphologic differences between the two groups. Therefore, data indicate that blood genotoxic stress occurs in birds of prey living in civil aviation areas as evidenced by MN frequency increase and presence of manganese and chromium.

Micronuclei induced by radiation, replication stress, or chromosome segregation errors do not activate cGAS-STING.

The cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a pivotal role in innate immune responses to viral infection and inhibition of autoimmunity. Recent studies have suggested that micronuclei formed by genotoxic stress can activate innate immune signaling via the cGAS-STING pathway. Here, we investigated cGAS localization, activation, and downstream signaling from micronuclei induced by ionizing radiation, replication stress, and chromosome segregation errors. Although cGAS localized to ruptured micronuclei via binding to self-DNA, we failed to observe cGAS activation; cGAMP production; downstream phosphorylation of STING, TBK1, or IRF3; nuclear accumulation of IRF3; or expression of interferon-stimulated genes. Failure to activate the cGAS-STING pathway was observed across primary and immortalized cell lines, which retained the ability to activate the cGAS-STING pathway in response to dsDNA or modified vaccinia virus infection. We provide evidence that micronuclei formed by genotoxic insults contain histone-bound self-DNA, which we show is inhibitory to cGAS activation in cells.

Small spaces, big problems: The abnormal nucleoplasm of micronuclei and its consequences.

Micronuclei (MN) form from missegregated chromatin that recruits its own nuclear envelope during mitotic exit and are a common consequence of chromosomal instability. MN are unstable due to errors in nuclear envelope organization and frequently rupture, leading to loss of compartmentalization, loss of nuclear functions, and major changes in genome stability and gene expression. However, recent work found that, even prior to rupture, nuclear processes can be severely defective in MN, which may contribute to rupture-associated defects and have lasting consequences for chromatin structure and function. In this review we discuss work that highlights nuclear function defects in intact MN, including their mechanisms and consequences, and how biases in chromosome missegregation into MN may affect the penetrance of these defects. Illuminating the nuclear environment of MN demonstrates that MN formation alone has major consequences for both the genome and cell and provides new insight into how nuclear content is regulated.

Evaluation of micronuclei, cytomorphometric and cytologic changes of the oral mucosa in hookah and cigarette smokers.

OBJECTIVE: To analyze the effect of hookah and cigarettes on the oral mucosa of smokers through the use of exfoliative cytology. STUDY DESIGN: Smear samples were collected by exfoliative cytology from the tongue of 33 hookah smokers, 22 cigarette smokers, and 30 non-smokers. The selected analyses include micronuclei (MN), metanuclear anomalies, epithelial maturation, and cytomorphology (nuclear area [NA], cytoplasmic area [CA], and NA/CA ratio). RESULTS: The largest differences observed for MN and metanuclear anomalies were between cigarette smokers and the control group (notably 1 MN P = .04; total cells with MN P = .039; total MN P = .042; karyorrhexis and binucleation, P = .0001). The hookah group, compared with the control group, showed the greatest differences for karyolysis (P = .0023), binucleation (P = .0003), and broken egg (P = .008). Significant differences were found between the smokers and the control groups regarding changes in the superficial cell without nucleus, perinuclear halo, vacuolization, color change, mucus, and keratohyalin granules. There was a significant increase in the NA and NA/CA ratio in the smoker groups. CONCLUSION: This study showed that a combined analysis of exfoliative cytology associated with other diagnostic methods is a useful tool for studying oral carcinogenesis. Hookah and cigarettes showed similar effects in terms of displaying substantial cytogenetic and cytotoxic damage.

Human plasma can modulate micronucleus frequency in TK6 and OE33 cells in vitro.

In this paper, we studied the potential genotoxic effects of human plasma from healthy volunteers, as well as patients with gastro-oesophageal reflux disease, Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) using the oesophageal adenocarcinoma cell line (OE33) and the lymphoblastoid cell line (TK6). Both TK6 and OE33 cells were treated with plasma (10 % volume, replacing foetal bovine serum (FBS) or horse serum (HS)) at different time points of 4 h (for the micronucleus (Mn) assay and the invasion assay) and 24 h (for the cell cycle studies). Plasma-induced effects on DNA damage levels, cell viability and the cell cycle were studied by the micronucleus assay, cytokinesis block proliferation index (CBPI) and flow cytometry respectively. The expression of IL-8 in supernatants of TK6 cells and IFN-ß in OE33 cells was also analysed by enzyme-linked immunosorbent assay (ELISA). Finally, we carried out an assessment of cellular invasion of OE33 cells following plasma treatment. The results of the micronucleus assay confirmed the genotoxicity of direct plasma treatment from some participants through the increase in DNA damage in TK6 cells. Conversely, some individual patient plasma samples reduced background levels of TK6 cell Mn frequency, in an anti-genotoxic fashion. In TK6 cells, (on average) plasma samples from patients with Barrett's oesophagus induced higher micronucleus levels than healthy volunteers (p= 0.0019). There was little difference in Mn induction when using plasma versus serum to treat the cells in vitro. Cell cycle results showed that direct plasma treatment had a marked impact on OE33 cells at 24 h (p=0.0182 for BO and p=0.0320 for OAC) by decreasing the proportion of cells in the S phase, while plasma exposure was less impactful on the cell cycle of TK6 cells. Invasion of OE33 cells was also seen to be non-significantly affected by plasma treatment of OE33 cells. The addition of N-acetyl cysteine NAC in a dose-dependent matter did not alter the formation of Mn in TK6 cells, suggesting that reactive oxygen species (ROS) are not the root cause of plasma's genotoxicity. The concentration of IL-8 in TK6 cells and IFN-ß in OE33 cells was significantly higher in cells treated with OAC-derived plasma than in the untreated negative control. Collectively, our results demonstrate that plasma-specific effects are detectable which helps us better understand some important aspects of the biology of blood-based biomarkers under development.

Chromosome-specific induction of micronuclei and chromosomal aberrations by mitomycin C: Involvement of human chromosomes 9, 1 and 16.

Cytogenetic studies have shown that human chromosomes 1, 9, and 16, with a large heterochromatic region of highly methylated classical satellite DNA, are prone to induction of chromatid breaks and interchanges by mitomycin C (MMC). A couple of studies have indicated that material from chromosome 9, and possibly also from chromosomes 1 and 16, are preferentially micronucleated by MMC. Here, we further examined the chromosome-specific induction of micronuclei (MN; with and without cytochalasin B) and chromosomal aberrations (CAs) by MMC. Cultures of isolated human lymphocytes from two male donors were treated (at 48 h of culture, for 24 h) with MMC (500 ng/ml), and the induced MN were examined by a pancentromeric DNA probe and paint probe for chromosome 9, and by paint probes for chromosomes 1 and 16. MMC increased the total frequency of MN by 6-8-fold but the frequency of chromosome 9 -positive (9+) MN by 29-30-fold and the frequency of chromosome 1 -positive (1+) MN and chromosome 16 -positive (16+) MN by 12-16-fold and 10-17-fold, respectively. After treatment with MMC, 34-47 % of all MN were 9+, 17-20 % 1+, and 3-4 % 16+. The majority (94-96 %) of the 9+ MN contained no centromere and thus harboured acentric fragments. When MMC-induced CAs aberrations were characterized by using the pancentromeric DNA probe and probes for the classical satellite region and long- and short- arm telomeres of chromosome 9, a high proportion of chromosomal breaks (31 %) and interchanges (41 %) concerned chromosome 9. In 83 % of cases, the breakpoint in chromosome 9 was just below the region (9cen-q12) labelled by the classical satellite probe. Our results indicate that MMC specifically induces MN harbouring fragments of chromosome 9, 1, and 16. CAs of chromosome 9 are highly overrepresented in metaphases of MMC-treated lymphocytes. The preferential breakpoint is below the region 9q12.

Micronuclei and other nuclear anomalies in exfoliated urothelial cells and urinary 8-hydroxy-deoxyguanosine levels among Turkish hairdressers.

Hairdressers are constantly occupationally exposed to many chemicals have the potential to cause allergies and carcinogenic effects, act as skin and eye irritants and induce oxidative stress and DNA damage. This study aimed to evaluate occupation-induced genotoxicity based on the presence of micronucleus (MN) and other nuclear anomalies in urothelial cells and measure oxidative DNA damage based on the 8-hydroxy-2'-deoxyguanosine level in the urine of Turkish hairdressers. Originality of this study comes from that there was no study on MN and other nuclear anomalies frequencies and oxidative DNA damage in urine samples of hairdressers in the literature. The mean±standard deviation frequency (‰) of micronucleated (MNed) cells was higher in the hairdresser group (n=56) (4.81±7.87, p<0.001) than in the control group (n=56) (0.93±1.85). Nuclear buds were not observed in either group. While the frequency of basal cells was higher in the control group (446.6±106.21) than in the hairdresser group (367.78±101.51, p<0.001), the frequency of binuclear, karyolytic, pycnotic and karyorrhectic cells were higher in the hairdresser group (0.41±0.80, p<0.001; 438.02±118.27, p<0.001; 0.43±0.76, p<0.001; and 47.27±28.40, p<0.001) than in the control group (0.04±0.27, 358.57±95.71, 0.05±0.23 and 24.41±14.50). Condensed chromatins were observed only in the hairdresser group. Specific gravity adjusted 8-hydroxy-2'-deoxyguanosine level was statistically lower in the hairdresser group (908.21±403.25 ng/mL-SG) compared to the control group (1003.09±327.09 ng/mL-SG) (p=0.024). No significant correlation was found between the 8-hydroxy-2'-deoxyguanosine level and the frequency MN. The amount of formaldehyde released during Brazilian keratin treatment was higher than the American Conference of Governmental Industrial Hygienists -Threshold Limit Value (ACGIH-TLV; 0.1 ppm). Similarly, the amount of ethyl acetate released in three salons was above the recommended limit (400 ppm). These findings suggest that hairdressers have an increased risk of genotoxicity and cytotoxicity owing to occupational exposure, regardless of age, working hours, smoking and alcohol consumption.