Micronuclei In Exfoliated Cells Research Articles

Salivary Oxidative Stress Assessment in Tobacco Users with and without Potentially Malignant Disorders and Micronuclei Estimation using Fluorescent Microscopy

Abstract Background: Consumption of tobacco in either smoking or nonsmoking form produces free radicals, contributing to an increased risk of oral cancer as a result of oxidative stress. Biochemical changes in antioxidant enzymes are responsible for tobacco-associated oral carcinogenesis. Due to the production of reactive oxygen species and oxidative stress, the promotion of carcinogenesis occurs in the cells. Oral potentially malignant disorders (OPMDs) is an assembly of benign lesions with morphologically altered clinical or histopathological tissue that has a greater than normal risk of transforming into malignant lesions after diagnosis at a later date. Micronuclei are the goal site for early genotoxic events and are involved in carcinogenic events. Micronuclei in exfoliated cells are useful biomarkers in assessing cytogenetic damage. Early detection will help to devise appropriate treatment plans, thereby improving patient survival rates. Aim and Objectives: To estimate the salivary superoxide dismutase (SOD) levels and the expression of micronuclei in exfoliated buccal cells of tobacco users before the onset of tobacco-induced oral lesions and correlating the same with patients with OPMDs to determine if this can be useful in predicting early malignant potential in subjects with habitual tobacco usage. Materials and Methods: The study included three groups. Group I – Tobacco users with OPMD (n = 50), Group II – Tobacco users without OPMD (n = 50), and Group III – Healthy controls (n = 50). Sandwich enzyme-linked immunosorbent assay was done for saliva samples for quantification of salivary SOD. Exfoliated buccal cells were smeared and stained with acridine orange stain and viewed under a fluorescent microscope for micronuclei estimation. Results: The study showed a significant difference in salivary SOD levels and increased micronuclei expression among tobacco users than healthy controls. Conclusion: Our study results revealed a gradual and steady decrease of SOD levels and increased micronuclei expression from healthy control to tobacco users without lesions and tobacco users with lesion, and this can be used as an effective noninvasive early diagnostic biomarker in assessing malignant progression in tobacco users. Furthermore, the evaluation of micronuclei estimation can serve as a simple, quick, and noninvasive chair-side procedure for regular oral cancer screening in patients with tobacco usage.

CONNOTATION OF MICRONUCLEUS AS A BIOMARKER IN CERVICAL INTRAEPITHELIAL LESIONS AND CARCINOMA

Introduction: The Pap smears study is the most rampant and cost-effective method for cervical cancer screening. The role of micronuclei in exfoliated cells of pap smears is the greater beneficial tool used in the screening of cervical cancers. They are intracytoplasmic inclusions made up of chromatin fragments that suggest instability in the chromosomes and they are found in great numbers in carcinogen-exposed tissues long before any clinical signs occur. Aims: To evaluate the predominance of Micronuclei as a biomarker in various premalignant and malignant lesions of cervixand to explore the association between various grades of cervical lesions and micronuclei frequency. Materials &Methods:A prospective study was done in the cytopathology section on 250 cervical pap smears collected in the Pathology laboratoryRajarajeswari medical college, Bangalore. The study period was from January 2021 to June 2021. Slides containing the cell material were stained with Papanicolaou stain, The results were analyzed as per the Micronuclei Scoring done per 1000 exfoliated squamous cells under light microscopy Results: In this study of 250 cervical pap smear screening, there was a stepwise gradual increase in micronuclei count(MN score)from Inflammatory lesions to carcinoma cervix. Inflammatory 2.04 ± 0.43, Atypicalsquamous cells of undetermined significance 3.9 ± 1.73, Atypical squamous cells - High grade5.64 ±1.83,Low grade squamous intraepithelial lesion 7.68 ±1.48, High grade squamous intraepithelial lesion08 12.32 ± 2.68and Intraepithelial Carcinoma 18.60 ± 2.83. Conclusion: MN scoring on cervix squamous epithelial cells is a simple and reliable objective test that may be performed on routine Pap-stained smears and can be used as adjunctive to the screening of cervical cancers and provide a potential pathway for disease monitoring in the future.

Bloom syndrome: an oral potentially malignant disorders aiding in malignancy vigour.

Bloom syndrome: an oral potentially malignant disorders aiding in malignancy vigour.

Quantification of micronuclei in exfoliated cells of human immunodeficiency virus/AIDS-infected female patients.

Background:Micronucleus (MN) is a biomarker for cytotoxicity, which is formed during cell division. Increased MN scoring has been successfully used to recognize population groups at risk for cancers of oral cavity, cervix, urinary bladder and esophagus. Incorporating MN score along with cytological smear testing gives a better and cost-effective screening for high-risk patients.Objective:This study evaluated the effectiveness of using MN score assessed from Papanicolaou (PAP) smears, as a biomarker for chromosomal damage in human immunodeficiency virus (HIV) patients.Materials and Methods:Oral smears of 25 female HIV/AIDS patients, without habits such as chewing or smoking tobacco, and taking antiretroviral therapy (ART) at ART center, were recruited for the study. After careful oral examination and oral rinsing with normal saline, smears were prepared on slides by scraping the buccal mucosa with a wooden spatula. All the slides were fixed in 95% ethyl alcohol and stained with PAP stain, and 1000 cells were counted per patient. Based on Tolbert et al.'s criteria, MNs were identified, and quantitative scoring of MN was done on the basis of morphological assay.Results:Mean ± standard deviation values of frequency of MNs in HIV-infected females were 73.40 ± 19.70 and in normal females were 38.08 ± 8.56.Conclusion:MN scoring on the epithelial cells of buccal mucosa can be used as a biomarker in screening procedures for HIV patients.

Utility of DNA-Specific Stains in Micronuclei Assay as a Marker of Genotoxicity in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma.

Background:The term oral potentially malignant disorder (OPMD) was recommended to refer to precancer as it conveys that not all disorders described under this term may transform into cancer. Oral squamous cell carcinoma (OSCC) arises through an accumulation of genetic alterations, deoxy ribonucleic acid (DNA) changes, and epigenetic alterations. Thus, a simple yet a sensitive and specific test for early diagnosis is the need of an hour. The micronuclei (MN) assay in exfoliated epithelial cells is potentially an excellent biomarker to detect chromosome loss or malfunction of mitotic spindle.Aim of the Study:To compare the frequency of MN in exfoliated cells from oral mucosa exposed to genotoxic agents using different staining procedures and to observe the incidence of micronucleus in potentially malignant and malignant lesions.Materials and Methods:The study was undertaken to observe the cytogenetic damage in the exfoliated buccal cells of 75 cases of tobacco-related PMDs, OSCC and control subjects (25 cases from each group) and were evaluated with nonspecific May-Grünwald Giemsa stain and DNA-specific Feulgen stain. The results were statistically determined using SPSS version 17.0.Results:Correlation analyses in the present study depicted that MN frequency was significantly more in oral squamous cell carcinoma than OPMDs and normal group (P < 0.05). Giemsa-stained slides correlated significantly with karyorrhexis, karyolysis, condensed chromatin, and binucleates, whereas no such correlations were found with DNA-specific stains.Conclusion:Malignant transformation is accompanied by loss of cell capacity to evolve to death in situations of DNA damage. These findings indicate that nuclear anomalies may be misinterpreted as MN with nonspecific DNA stains and lead to false-positive results in studies with cells of epithelial origin.

Micronuclei in Exfoliated Cells: A Biomarker of Genotoxicity in Tobacco Users.

Aims:The aim of this study was to analyze the tobacco-related genotoxic effects in individual with habit of smoking and chewing tobacco.Materials and Methods:The present study sample consisted of 120 individuals attending the outpatient department of D. J. College of Dental Sciences and Research, Modinagar, Uttar Pradesh (UP). The sample was divided into four groups as follows: Group I (individuals with habit of smoking tobacco), Group II (individuals with habit of chewing tobacco), Group III (individuals with habit of smoking and chewing tobacco), and Group IV control group (nontobacco-exposed individuals). Patients were asked to rinse their mouth gently with water. The exfoliated cells were obtained by scraping the buccal mucosa of individuals with a wooden spatula. The scraped cells were placed on the precleaned slides. The smears were then stained with RAPID-PAP™ and analyzed under the microscope. Data were analyzed using SPSS statistical software.Results:In the present study, an arbitrary unit was obtained using frequency/day multiplied by the duration of years (risk multiplication factor [RMF], a positive and significant correlation were observed between the RMF and the mean percentage of micronucleated cell count in smokers, chewers, and in individuals with both smoking and chewing habit, respectively. A weak positive and nonsignificant correlation were observed between age and mean percentage of micronucleated cells in smokers and smokers + chewers, respectively, while it was weak negative and nonsignificant in chewers. In control group, correlation between age and percentage of micronucleated cells was weak positive and nonsignificant at 5% level of significance.Conclusion:The micronuclei in exfoliated mucosal cells from buccal mucosa can be used as a biomarker of genotoxicity in predicting the effects of carcinogens.

Evaluation of Pb-210 in urine and frequency of micronuclei in exfoliated cells as indicators of exposure to cigarettes

This study aimed at analyzing the frequency of micronuclei (MN) in exfoliated cells as well as the levels of Pb-210 in urine samples to evaluate the association between the smoking habit and toxic stress of transitional epithelial cells. The frequency of MN was scored from Giemsa-stained slides while exchange resin and beta counting techniques were employed to measure the concentrations of this radioisotope. Urine samples of smokers had levels of Pb-210 up to 158.65 mBq L−1. For nonsmokers, the median was below the detection limit (45 mBq L−1). The analyses of mononucleated cells showed a significant increase of the frequency of MN in smokers when compared to nonsmokers. Statistical tests showed a tight relation between the cigarette consumption and the increase of the frequency of MN, rather than with the levels of Pb-210 present in smoke particles. The results indicate the usefulness of the methodology for the evaluation of human health risks related to chronic contamination with Pb-210.

Micronuclei as prognostic indicators in oral cytological smears: A comparison between smokers and non-smokers

Background: Micronucleus is a microscopically visible round or oval cytoplasmic chromatin mass in the extra nuclear vicinity, originated from aberrant mitosis, which consists of eccentric chromosomes that have failed to reach spindle poles during mitosis and are used as biomarkers for assessment of DNA damage. Micronuclei are characteristically seen in exfoliated cells of the buccal mucosa and urinary bladder wall in precancerous and cancerous conditions. Oral habits of smoking tobacco or chewing areca nut damage the oral tissues. An assessment of the damage is feasible by the detection of micronuclei in exfoliated cells of the oral tissues using smears. Objectives: The present study was designed to assess the presence or increase of micronuclei in buccal smears of individuals with tobacco habits against a control group of teetotalers. Materials and Methods: Two groups (smokers and non-smokers) of 50 individuals each were examined. Buccal smears of all participants were taken using cytobrush and stained with standard Papanicolaou's (PAP) stain. Presence of micronuclei was assessed under Χ100 magnification and a count per 500 cells was determined. The results were analyzed statistically using t-test and Mann-Whitney test. Results: Smears of individuals with tobacco habits showed a significant increase in the total number of micronuclei per 500 cell counts. There was a definite correlation between the occurrence of micronuclei and the frequency and duration of smoking. A paradoxical age related increase in middle-aged groups was also observed. Conclusions: The genotoxic effects of tobacco smoke cause chromosomal damage in the epithelial cells of the oral mucosa and are reflected in the increased micronuclei in smokers. This is present even in the absence of clinically evident changes. This observation is vital in utilization of the micronuclei detection in smears as a prognostic, educational and interventional tool in the management of patients with smoking habits.

Evaluation of micronuclei in tobacco users: A study in Punjabi population

Introduction:The assessment of micronuclei in exfoliated cells is a promising tool for the study of epithelial carcinogens and can be used to detect chromosome breakage or mitotic interference, thought to be relevant to carcinogenesis.Aim:The present study aimed to detect micronuclei in exfoliated oral mucosal cells in individuals using various tobacco forms from the last 5 years.Materials and Methods:A total of 75 healthy male subjects (25 smokeless tobacco users, 25 smokers, and 25 non–tobacco users) were selected for the study. Smears were obtained with moistened wooden spatula from buccal mucosa and fixed with 95% alcohol. All the cytologic smears were stained by Papanicolaou technique. From each slide, ~1000 cells were examined under the 400× magnification and where micronucleated (MN) cells were located, they were examined under the 1000× magnification.Result:MN cells were found to be significantly higher in smokeless tobacco users than in smokers and controls.Conclusion:A positive correlation is found between increased micronucleus frequency and tobacco-using habits. So micronucleus assay can be used as a biomarker of genotoxicity.

Short Communication Genotoxic effects caused by indoor exposure to petroleum derivatives in a fuel quality control laboratory

We looked for genotoxic effects in laboratory personnel routinely exposed to petroleum derivate compounds in an indoor environment. The exposed group of 21 workers from the Fuel Quality Control Laboratory of the Brazilian Petroleum Agency was matched with a group of 10 people from the staff of the Brazilian Ministry of Health. Chromosome aberrations in peripheral blood lymphocytes, micronuclei in exfoliated cells in the urine and hematological parameters were examined. There was a significantly increased level of chromosome aberrations and micronuclei in the exposed group compared with controls. A high correlation between chromosome aberrations and micronuclei was observed in the exposed group (Spearman rank test, r = 0.73, P = 0.0001). The hematological parameters in these exposed individuals did not differ from reference values.

Genotoxic effect of ethanol on oral mucosa cells

Ethanol is one of the chemicals related to the development of oral malignant neoplasms. Micronuclei are chromatin fragments which, after aberrant mitoses, do not become included in the main nucleus. They have been used as indicators of genotoxic damage in cells exposed to carcinogens. The aim of this study was to assess the frequency of micronuclei in exfoliated cells from the tongue and buccal mucosa of alcoholic individuals. Samples were taken from the tongue and buccal mucosa of 40 alcoholic individuals who did not smoke, and from 20 alcohol and tobacco abstainers. Cells were stained with the Feulgen reaction and counterstained with Fast Green. A significant increase in the frequency of micronuclei in tongue cells was found in the group of subjects exposed to alcohol, when compared to the control group (p < 0.01). The frequency of micronuclei in buccal mucosa cells was higher in the group of alcoholic individuals, when compared to the control group, although there was no significant difference (p > 0.05). Our results indicate that excessive alcohol consumption may induce effective alterations on oral mucosa cells, even without exposure to tobacco. These alterations are more expressive in the tongue, which is a site more exposed to the action of carcinogens, when compared to the buccal mucosa.

Use of the fluorescent micronucleus assay to detect the genotoxic effects of radiation and arsenic exposure in exfoliated human epithelial cells

The exfoliated cell micronucleus (MN) assay using fluorescent in situ hybridization (FISH) with a centromeric probe is a rapid method for determining the mechanism of MN formation in epithelial tissues exposed to carcinogenic agents. Here, we describe the use of this assay to detect the presence or absence of centromeric DNA in MN induced in vivo by radiation therapy and chronic arsenic (As) ingestion. We examined the buccal cells of an individual receiving 6,500 rads of photon radiation to the head and neck. Exfoliated cells were collected before, during, and after treatment. After radiation exposure a 16.6-fold increase in buccal cell MN frequency was seen. All induced MN were centromere negative (MN −) resulting from chromosome breakage. This finding is consistent with the clastogenic action of radiation and confirmed the reliability of the method. Three weeks post-therapy, MN frequencies returned to baseline. We also applied the assay to exfoliated bladder cells of 18 people chronically exposed to high levels of inorganic arsenic (In-As) in drinking water (average level, 1,312 μg As/L) and 18 matched controls (average level, 16 μg As/L). The combined increase in MN frequency was 1.8-fold (P = 0.001, Fisher's exact test). Frequencies of micronuclei containing acentric fragments (MN −) and those containing whole chromosomes (MN+) both increased (1.65-fold, P = 0.07, and 1.37-fold, P = 0.15, respectively), suggesting that arsenic may have both clastogenic and weak aneuploidogenic properties in vivo. After stratification on sex, the effect was stronger in male than in female bladder cells. In males the MN-frequency increased 2.06-fold (P = 0.07) while the frequency of MN+ increased 1.86-fold (P = 0.08). In addition, the frequencies of MN − and MN+ were positively associated with urinary arsenic and its metabolites. However, the association was stronger for micronuclei containing acentric fragments. By using FISH with centromeric probes, the mechanism of chemically induced genotoxicity can now be determined in epithelial tissues. © 1996 Wiley-Liss, Inc.

Evaluation of frequency of micronuclei in exfoliated cells from bladder of mice treated with benzo(a)pyrene, 2-acetylaminofluorene and cyclophosphamide.

The micronucleus test (MNT) was applied in the epithelial cells from the bladder of mice treated with benzo(a)pyrene (BaP), 2-acetylaminofluorene (2-AAF) and cyclophosphamide (CP). Micronuclei (MN) were scored at different time on Feulgen and fast green stained smear preparations of exfoliated cells. These cells were obtained by scraping the internal surface of the bladder. The tested compounds gave the maximal response at 7-10 days after treatment. The number of MN in epithelial cells was dose dependent. These results suggest that exfoliated bladder cells from mice can be used as indicators for genotoxic damage in proliferating cell populations.

Localized induction of micronuclei in the oral mucosa of xeroderma pigmentosum patients

Xeroderma pigmentosum (XP) patients are predisposed not only to skin cancers but also to tumors on the tip of the tongue. Although this enhanced risk has been attributed to a defect in the repair of DNA damage induced by ultraviolet rays from sunlight there is a lack of data showing that DNA damage is occurring in vivo at these sites. In order to determine whether a relationship exists between exposure to ultraviolet light and the level of chromosomal breakage occurring in epithelial tissue in XP patients, the exfoliated cell micronucleus test was applied to different sites in the oral cavities of four XP patients: the right and left buccal mucosa, the dorsal tip of the tongue and the palate. Six Egyptian controls were sampled concurrently. Micronucleus (MN) frequencies were higher in XP patients than in controls for all sites except the palate, where technical difficulties were encountered. In addition, an unequal distribution of the frequency of micronucleated cells was found in the different sample sites of the oral cavity in the XP patients, with the greatest elevation in frequencies among cells collected from the dorsal tip of the tongue. In contrast, the frequency of micronucleated cells did not vary significantly in samples from different sites obtained from the controls. These data suggest that the complex interplay of host and environmental factors can affect MN frequencies when this endpoint is used to quantify in vivo genotoxic damage in a tissue.

Novel biomarkers of genetic damage in humans: use of fluorescence in situ hybridization to detect aneuploidy and micronuclei in exfoliated cells.

Here we describe new techniques that employ fluorescence in situ hybridization (FISH) with centromeric and chromosome-specific DNA probes to detect aneuploidy and micronucleus formation in exfoliated human epithelial cells. Micronuclei arise from chromosome breakage or lagging, which results in chromosome fragments and whole chromosomes being left outside of the main nucleus at telophase. By using a centromeric DNA probe to detect the presence of whole chromosomes in micronuclei and propidium iodide as a general DNA stain in exfoliated nasal, buccal, and bladder cells, we have developed a new fluorescent method that can detect micronuclei and determine the mechanism of formation. The new fluorescent technique gave results that were very similar to those obtained with the standard Feulgen-fast green method. The spontaneous levels of micronuclei in healthy volunteers were buccal, 0.13%, nasal, 0.21%, and urothelial, 0.07%, in approximately 1500 cells per data point. These values are lower than that found in cultured lymphocytes, 0.4-0.8%. Approximately 50% of the exfoliated cell micronuclei contained whole chromosomes (centromeric DNA). FISH was also used to detect aneuploidy in exfoliated buccal and bladder cells. A DNA probe specific for chromosome 9 was used. Average frequencies for 0, 1, 2, 3, and 4 hybridization regions were 4.8, 9.3, 84.8, 0.8, and 0.3% for urothelial cells and 8.2, 9.9, 80.1, 1.4, and 0.4% for buccal cells. The estimated frequency of aneuploidy in exfoliated cells is similar to that found in human lymphocytes analyzed by FISH with the same probe for chromosome 9. These techniques are potentially useful for epidemiological studies of exposed populations and are currently being applied in our laboratory for studies of arsenic- and formaldehyde-exposed populations.

Micronuclei and other nuclear anomalies in buccal smears: methods development

Laboratory work aimed at improving the epidemiologic utility of an innovative genotoxicity assay is described. The exfoliated cell micronucleus assay involves microscopic analysis of epithelial smears to determine the prevalence of micronucleation, an indicator of structural or numerical chromosome aberrations. While the assay holds promise for the study of epithelial carcinogens, it is hampered by the fact that exfoliated cells are moribund and undergo degenerative phenomena that can produce extranuclear objects difficult to distinguish from classical micronuclei. Modifications in the protocol were assessed in sample buccal smears from several study populations: radiotherapy patients, nonusers of tobacco, and snuff users. Refinements in micronucleus scoring criteria and the inclusion of other nuclear anomalies in the scoring system are proposed. We demonstrate that our criteria are successful in detecting excess micronucleation in positive controls. We also provide evidence that other nuclear anomalies are at least as common as micronucleation and that therefore there is the potential for extensive misclassification. Reliability was assessed in duplicate readings.

Micronuclei and Other Nuclear Anomalies in Buccal Smears: A Field Test in Snuff Users

A revised protocol for the exfoliated cell micronucleus assay was field-tested in a population exposed to a genotoxic agent, snuff, at levels associated with a significant increase in cancer risk. The standard assay involves examination of epithelial smears to determine the prevalence of micronucleated cells, an indication of chromosome breakage or mitotic interference. The assay was revised to increase specificity and to include separate scoring of other nuclear anomalies associated with cytotoxicity and genotoxicity. The modified assay was applied to buccal smears of 38 female snuff users and 15 female nonusers recruited from a North Carolina clinic in 1987. The prevalence of micronucleation was elevated in the snuff users as compared with the nonusers (prevalence ratio = 2.4, 95% confidence interval 1.1-5.2) and, to a lesser extent, at the usual contact site as compared with a distal buccal site in the snuff users (prevalence ratio = 1.5, 95% confidence interval 0.9-2.5). The pattern of relative frequencies of several nuclear anomalies provided strong evidence of a cytotoxic effect, the prevalence ratios ranging from 2 to 13. Nuclear degenerative phenomena can be difficult to distinguish from classical micronuclei; thus, the observed association of indicators of cytotoxicity with exposure introduces the possibility of bias away from the null in micronucleus findings due to differential misclassification. Until methods to better distinguish extranuclear bodies of different origins become available, investigators should use the revised protocol and should focus on agents not thought to be cytotoxic.

Leather tanning workers: chromosomal aberrations in peripheral lymphocytes and micronuclei in exfoliated cells in urine

A cytogenetic study was performed on workers of a leather tanning industry. Two different approaches for the biological monitoring of the individuals were used: chromosomal aberration analysis in peripheral lymphocytes and the frequency of micronucleated cells exfoliated in urine samples. 26 men working in the sections considered to present a greater risk were included in the study. Controls were 20 men that were not exposed to chemicals. The percentage of abnormal cells was higher in workers than in controls. Smokers showed higher values of chromosome breaks than non-smokers in both groups. These differences were not statistically significant. The percentage of cells with chromatid and chromosome gaps in workers and controls was different ( p < 0.01). A slight but not significant increase in the mean percentage of micronuclei was observed in the exposed group. We conclude that exposure to chemicals during leather tanning did not produce genotoxic effects measured by chromosomal aberrations in peripheral lymphocytes and micronuclei in urine in this group of workers.

Evidence for chromosome instability in vivo in Bloom syndrome: increased numbers of micronuclei in exfoliated cells.

The incidence of exfoliated epithelial cells containing micronuclei was determined in two small human populations, one homozygous and the other heterozygous for the Bloom syndrome gene (bl). The objectives of the study were two: to learn whether the chromosome instability featured so prominently by Bloom syndrome (BS) cells proliferating in vitro also occurs in vivo, and as part of a broad survey of various cancer-prone populations, to determine whether estimating micronucleus frequencies in exfoliated cell samples might be useful for identifying individuals with genetically determined chromosome instability. Eight individuals homozygous (bl/bl) for the BS gene, i.e., persons with the clinical syndrome, were examined, along with 11 obligate heterozygotes (bl/+), parents of affected persons. Exfoliated cells were obtained from two sites, the oral cavity and the urinary tract. Striking and statistically highly significant elevations in the frequencies of cells with micronuclei were observed in cells from both sites in bl/bl individuals compared to that in bl/+ (P less than 0.001) and in a control population, indicating that chromosome instability occurs in vivo in BS. In contrast, micronucleus frequencies at either site did not differ significantly between bl/+ individuals and the control population. This survey, in combination with similar earlier ones of populations predisposed to cancer not on a genetic basis but because of exposure to some environmental carcinogen, suggests that the exfoliated cell micronucleus test identifies individuals whose somatic genetic material has, for either genetic or environmental reasons, been damaged in a way that produces chromosome breakage and rearrangement.