Chromosomal aberrations analysis in a Brazilian population exposed to pesticides

In spite of being harmful, pesticides are widely used in Brazil. Their genotoxic effects might be studied through population monitoring by means of the analysis of chromosomal aberrations in occupationally exposed individuals. The aim of this study was to evaluate the chromosomal aberration frequencies in temporary cultures of lymphocytes from periferic blood of 23 workers professionally exposed to a mixture of pesticides. The workers were employed by the Agronomic Institute of Parana (Brazil) and used all of the prevention measures provided. A detailed history of pesticide use, as well as personal data, smoking habits, and history of recent illnesses and medical treatment were collected through a standardized questionnaire administered to each subject. Nonexposed subjects, matched for age, sex, and smoking habits, served as the negative control. A total of 100 cells were analyzed from each individual. A significant increase in chromosomal aberration frequencies was observed in exposed individuals when compared to the control group. Some individual characteristics such as age, sex, time of exposure to the pesticides, and smoking habits showed no correlation with chromosomal aberrations. Therefore, the positive results may be considered true effects of pesticides on human somatic cells.     

Genotoxic evaluation of welders occupationally exposed to chromium and nickel using the Comet and micronucleus assays

Chromium (Cr) and nickel (Ni) are widely used industrial chemicals. Welders in India are inclined to possible occupational Cr and Ni exposure. The carcinogenic potential of metals is a major issue in defining human health risk from exposure. Hence, in the present investigation, 102 welders and an equal number of control subjects were monitored for DNA damage in blood leucocytes utilizing the Comet assay. The two groups had similar mean ages and smoking prevalences. A few subjects were randomly selected for estimation of Cr and Ni content in whole blood by inductively coupled plasma mass spectrometry. The Comet assay was carried out to quantify basal DNA damage. The mean comet tail length was used to measure DNA damage. Welders had higher Cr and Ni content when compared with controls (Cr, 151.65 versus 17.86 micro g/l; Ni 132.39 versus 16.91 micro g/l; P < 0.001). The results indicated that the welders had a larger mean comet tail length than that of the controls (mean +/- SD, 23.05 +/- 3.86 versus 8.94 +/- 3.16; P < 0.001). In addition, the micronucleus test on buccal epithelial cells was carried out in a few randomly selected subjects. Welders showed a significant increase in micronucleated cells compared with controls (1.30 versus 0.32; P < 0.001). Analysis of variance revealed that occupational exposure (P < 0.05) had a significant effect on DNA mean tail length, whereas smoking and age had no significant effect on DNA damage. The current study suggested that chronic occupational exposure to Cr and Ni during welding could lead to increased levels of DNA damage.     

Cytogenetic monitoring of hospital workers occupationally exposed to ionizing radiation using the micronucleus centromere assay

A cytogenetic study was performed in lymphocytes of hospital workers occupationally exposed to X- and gamma-rays using the micronucleus centromere assay. A comparison of the data for the exposed group and an age-matched group of non-exposed hospital workers showed a significant (P < 0.05) increase in centromere-positive micronuclei for the radiation workers, while no effect on centromere-negative micronuclei was present. The observed systematic increase in micronucleus frequency with age was mainly due to increased chromosome loss, reflected in the centromere-positivity of the micronuclei. The micronucleus frequencies were 40% higher in females than in males, which can again be attributed to higher chromosome loss. Two exposed individuals showed exceptionally high micronucleus yields, 90% of which were centromere-positive. In situ hybridization with a centromeric probe for chromosome X shows that X chromosome loss is responsible for these high micronucleus yields. In the studied population, smoking had no significant effect on the micronucleus yields. The results obtained indicate that in contrast to the predominantly clastogenic action of acute exposure to ionizing radiation, the aneugenic properties of radiation may be important after long-term chronic low dose exposure.     

Comparison of chromosome aberrations in peripheral blood lymphocytes from people occupationally exposed to ionizing and radiofrequency radiation

The genotoxic effects of occupational exposure to ionizing and non-ionizing radiation were investigated in 25 physicians and nurses working in hospitals and in 20 individuals working at radio-relay stations. Examination was conducted by chromosome aberration analysis of peripheral blood lymphocytes. The data showed that total number of chromosome aberrations in people exposed to ionizing and radio-frequency radiation (4.08 +/- 0.37 and 4.35 +/- 0.5 on 200 scored metaphases, respectively) were almost equally higher than those of non-irradiated subjects. The increase was in proportion to the number of individuals having more that 5-aberration/200 metaphases. Acentric fragments comprised the most frequently seen type of aberration. The average numbers in examined groups (11.8 x 10(-3) and 14.8 x 10(-3) per cell, respectively), were significantly higher than 4.2 x 10(-3), which was observed in controls, unexposed individuals. Dicentric fragments were also frequent (4.8 x 10(-3) and 6.25 x 10(-3), respectively, vs. 0.52 x 10(-3) in control). In contrast, the frequency of chromatid breaks increased only after ionizing radiation (3.8 x 10(-3) vs. 0.26 x 10(-3) in control). A positive correlation between the total number of chromosome aberrations and cumulative 6-years dosage was also found. The data emphasized the dangerous effects of prolonged exposure to both types of radiation and indicated that chromosomal aberration analysis should be obligatory for individuals working at radio-relay stations.     

Chromosomal aberrations in the cotton rat, Sigmodon hispidus, exposed to hazardous waste

The study of chromosome damage in rodents living on hazardous-waste sites may provide evidence of important biological consequences of chronic exposure to toxic chemical wastes. This study compared bone-marrow cells of animals (Sigmodon hispidus) taken from two superfund waste-disposal sites with those from an uncontaminated site and demonstrated that both populations exposed to hazardous wastes had significantly more structural and numerical aberrations than the control population.     

Chromosomal aberrations and micronuclei in lymphocytes of patients before and after exposure to anti-tuberculosis drugs

To evaluate the genetic damage induced by tuberculosis infection and also by a combination of therapeutic exposure to anti-tuberculosis (anti-TB) drugs (isoniazid + rifampicin + pyrazinamide + ethambutol or streptomycin) we have considered chromosome aberrations (CA) and micronuclei (MN) in binucleate peripheral blood lymphocytes from 36 patients diagnosed with pulmonary tuberculosis prior to receiving anti-TB drugs in the first phase and in the second phase after 6 months of therapy with anti-TB drugs. The same cytogenetic study has also been performed on 36 healthy individual controls. It was shown that the frequencies of both CA and micronucleated binucleate cells increased significantly after therapy with anti-TB drugs as compared with TB patients and controls. In addition, we observed that both cytogenetic markers (CA and MN) in patients before treatment with anti-TB drugs were significantly (P: < 0.05) higher than controls. No relationship was found between the frequency of MN and donor age. Thus, apart from drug effects, infection with tuberculosis is associated with increased CA and MN.     

Increased frequency of chromosomal aberrations in industrial painters exposed to lead-based paints

The investigation was carried out in the peripheral lymphocytes of industrial painters who were exposed to dust and fumes of lead-based paints. Samples of peripheral blood were collected from 102 workers out of which 40 were smokers and 62 were nonsmokers. The painters in both the categories were divided in to 3 groups based on duration of exposure. Control data of 30 nonsmokers and 20 smokers belonging to the same socioeconomic group but not exposed to either radiation or toxic chemicals were studied. There was a significant increase in the frequency of chromosomal aberrations in the workers when compared to the controls. Further, smoking had an added effect on the frequency of aberrant metaphases.     

A follow-up study on micronucleus frequency in Spanish agricultural workers exposed to pesticides.

To determine whether occupational exposure to a complex mixture of pesticides results in a significant increase in the level of cytogenetic damage, a follow-up study was planned on 39 greenhouse workers from Almería (southeastern Spain). Taking into account that pesticide exposure can be season-related, two blood samples were taken from each individual at different times: one in a period of high exposure (sample A, spring-summer) and the other in a period of lower exposure (sample B, autumn-winter). Using the cytokinesis block micronucleus technique the frequency of binucleated cells with micronuclei (BNMN) and the cytokinesis blocked proliferation index (CBPI) were determined in peripheral blood lymphocytes. The results obtained indicate that there were no statistically significant differences in BNMN frequencies between the two sampling periods nor between exposed and controls. ANCOVA analysis of repeated measures revealed that the age of the individuals showed a direct relation with BNMN in the first study period. With regard to CBPI, a significant and season-related effect was found.     

A cytokinesis-blocked micronucleus study of the radioadaptive response of lymphocytes of individuals occupationally exposed to chronic doses of radiation

Human lymphocytes pre-exposed to very low doses of ionizingradiation show an adaptive response, which make these cellsless sensitive to subsequent higher exposures. To verify thehypothesis that a similar phenomenon can be induced by occupationally(in vivo) received doses of ionizing radiation, the cytogeneticresponses of 24 medical radiation workers to 1 and 2 Gy     

Chromosomal aberrations in infective hepatitis

Structural chromosomal aberrations, in the form of breaks, were found in a significantly higher proportion of bone marrow cells in patients with infective hepatitis than in controls. These anomalies were observed during the first and third weeks after the onset of jaundice but had subsided by the sixth week.Chromosomal aberrations did not appear to be related to the severity of infective hepatitis or to the sex or age of the patients.The distribution of chromosomal abnormalities did not appear to be random; they were observed predominantly in the A(2) and B(4-5) series. Since no abnormalities were detected in the G-group chromosomes, no evidence in support of a relationship between infective hepatitis and Down's syndrome was obtained.Numerical chromosomal aberrations were not observed, nor was any evidence obtained that mitotic activity of bone marrow cells is suppressed in patients with infective hepatitis.     

Genotoxicological investigation of hospital nurses occupationally exposed to ethylene-oxide: I. Chromosome aberrations,sister-chromatid exchanges,cell cycle kinetics,and UV-induced DNA synthesis in peripheral blood lymphocytes

Structural, and numeric chromosome aberrations (CA), sister-chromatid exchange (SCE), phytohemagglutinin stimulation (U), proliferative rate index (PRI), and UV light-induced unscheduled DNA-synthesis (UDS) were investigated in peripheral blood lymphocytes (PBL) of 48 historical controls (“Controls”); of 14 hospital controls in Budapest, Hungary (“Budapest controls”); of 9 nurses occupationally exposed to low-dose ethylene-oxide (ETO) in Budapest (“Budapest exposed”); of 10 hospital controls in Eger, Hungary (“Eger controls”); and of 27 high dose ETO-exposed nurses in Eger (“Eger exposed”), where neoplasias, mainly breast cancers, were observed. ETO concentrations in the ambient air samples varied from 5 to 20 mg/m³ in Budapest; and from 5 to 100 mg/m³ in Eger. Both LI and PRI were depressed in Budapest exposed, indicating ETO-induced cytotoxicity and, however, normal in Eger exposed. SCE was slightly elevated in Budapest exposed, but significantly increased in Eger exposed. The yields of cells with high frequency SCE (HFC) were only increased in Eger exposed. The expected low CA frequencies were found in Controls and in Budapest controls. ETO exposures significantly increased the CA frequencies in Budapest and Eger exposed. In Budapest exposed, as expected, we found deletions; in a lesser extent chromatid exchanges and dicentrics; but no rings were detected. These results are in a good accordance to the published data of other investigations carried out on ETO-exposed human populations. However, in Eger exposed, beside the increased yields of deletions, the frequencies of dicentrics and rings showed a significant excess compared to the reviewed data. An unexpected, significant increase of dicentric and ring frequencies was also detected among the hospital controls in Eger controls without known clastogenic exposure. The role of confounding factors (age, smoking and drinking habit, total leukocyte count and hematocrit) was investigated by an analysis of variance on CA and SCE frequencies in Controls and in Eger exposed. Leukocyte count and mean age showed only significant effects on CA in Eger exposed and on SCE in Controls, respectively. A possible active confounding factor could be the temporary natural radioactivity of the local top water. UDS in Budapest exposed and in Eger control were significantly higher then in the Controls and in Budapest controls. In Eger exposed UDS was significantly decreased compared to the Budapest exposed and Eger control groups. The explanation of the present results is difficult on the basis of the reviewed data on ETO-induced CA frequencies in exposed human populations, and it raises an issue of an independent genotoxic effect in Eger, which is common both in Eger controls and in Eger exposed, such as natural radioactivity. © 1996 Wiley-Liss, Inc.     

Cytogenetic study in workers occupationally exposed to mercury fulminate

This study was conducted to evaluate the cytogenetic effects in male workers exposed to mercury fulminate. A total of 29 male workers and 29 age- and sex-matched controls were examined. The mean mercury level in urine from the exposed workers was 123.2 +/- 54.1 micrograms/l compared with 39.2 +/- 11.1 micrograms/l in the control group. The difference was statistically significant (P less than 0.001). Metaphase chromosomes were studied. Micronucleated peripheral blood lymphocytes were also analyzed in cytochalasin B blocked binucleated lymphocytes. The percentage of metaphases with chromosomal aberrations was significantly higher (P less than 0.001) in the exposed group (6.1 +/- 2.3) compared to the control group (2.8 +/- 0.7). The chromosomal aberrations detected were in the form of gaps, breaks and fragments. A significant increase in the incidence of micronucleated lymphocytes was found among the exposed group (7.1 +/- 4.2) compared to the control group (5.4 +/- 2.2) (P less than 0.01). The detected chromosomal damage correlated neither with the duration of exposure nor with the urinary mercury level.     

Chromosomal aberrations in young cancer patients

Spontaneous level of chromosomal aberrations (CA) is considered to be indicative of inherent cancer predisposition, which plays a major role in total cancer incidence. We have studied spontaneous CA levels in in vitro cultured peripheral blood lymphocytes of pediatric cancer patients (n = 77). Results were compared with those of control subjects (n = 72), including: age-matched controls; elder controls (minimum age 60 years); and healthy first-degree relatives (FDR) of pediatric cancer patients. Pediatric cancer patients showed the highest mean CA/cell value, which was statistically significant as compared to their age-matched counterparts, elder controls, and the FDRs. As compared to 7% of all the three control groups collectively, 32.4% of pediatric cancer patients showed > 0.1 mean CA/cell value. One of the FDRs with a very high frequency of CA developed cancer within three years. The results suggest that spontaneous levels of chromosomal aberrations may be used as one of the biomarkers for cancer predisposition study.     

Alterations in leukocyte telomere length in workers occupationally exposed to benzene

Exposure to benzene, a known leukemogen and probable lymphomagen, has been demonstrated to result in oxidative stress, which has previously been associated with altered telomere length (TL). TL specifically has been associated with several health outcomes in epidemiologic studies, including cancer risk, and has been demonstrated to be altered following exposure to a variety of chemical agents. To evaluate the association between benzene exposure and TL, we measured TL by monochrome multiplex quantitative PCR in 43 workers exposed to high levels of benzene and 43 age and sex‐matched unexposed workers in Shanghai, China. Benzene exposure levels were monitored using organic vapor passive dosimetry badges before phlebotomy. The median benzene exposure level in exposed workers was 31 ppm. The mean TL in controls, workers exposed to levels of benzene below the median (≤31 ppm), and above the median (>31 ppm) was 1.26 ± 0.17, 1.25 ± 0.16, and 1.37 ± 0.23, respectively. Mean TL was significantly elevated in workers exposed to >31 ppm of benzene compared with controls (P = 0.03). Our findings provide evidence that high levels of occupational benzene exposure are associated with TL. Environ. Mol. Mutagen. 55:673–678, 2014. Published [2014]. This article is a U.S. Government work and is in the public domain in the USA.     

Chromosomal aberrations in premalignant and malignant squamous epithelium

Biopsies of oropharyngeal cancer were screened for chromosomal imbalances by comparative genomic hybridization (CGH) performed on 22 primary tumors and morphologically nonmalignant surrounding mucosa. The aim was to determine early chromosomal changes of tumor development and to draw conclusions on the mechanisms leading to multiple tumors. The most prominent chromosomal imbalances observed were over representations of genomic material on 3q, 15q, 8q, and 11q and losses on 9p, 3p, and 11q. In morphologically normal mucosa collected at 1 cm from the primary tumor border (M1), amplifications on 15q and 21q were most frequent. Far fewer gains and losses were found in M1 than in the primary tumor (average 2.2 vs. 6.9). Gains dominated over losses, but a tendency toward an increasing proportion of losses in the primary tumor (PT) was observed (ratio of gains to losses: PT, 4.75; M1, 6.3). Almost all the imbalances in M1 were detected in the primary tumor. No chromosomal alterations were identified with CGH in tissue samples dissected at 2 cm from the primary tumor (M2). In all samples, dysplastic morphologic changes decreased with distance from the primary tumor, which correlates with the observed lower level of genetic changes. We suggest that gains of genetic material on 15q and 21q are early events in malignant progression of squamous cell carcinoma, followed by gains on 3q, 8q, and 11q, and losses on 3p and 9p at later stages. Based on our cytogenetic data, we discuss the monoclonal model followed by lateral epithelial spread as an explanation of multiple head and neck squamous cell carcinomas.     

Sensitization and lung function in workers occupationally exposed to natural thickening products

BACKGROUND: Three workers engaged in the manufacture of natural thickener products (Cassia spp., guar, and tamarind flour) were occupationally sensitized to Cassia spp. Therefore, a cross-sectional study on the prevalence of sensitization among and respiratory health of the employees of this plant was conducted. METHODS AND RESULTS: Sixty-two workers (36 with high, 26 with low exposure) participated in the survey. Skin prick tests and specific IgE tests with extracts of these components revealed that 11.3% were sensitized to Cassia spp. and 9.7% to at least one species of storage mites, with a significantly higher portion of atopic subjects in the sensitized group. Overall, 55% of the subjects reported work-related symptoms (upper and lower airways, eyes, or skin). FVC % pred. was significantly lower in highly exposed workers, while RV % pred. and RV%TLC % pred. were significantly higher in this group. In the multivariate model, sensitization was not a risk factor for impairment of lung function. CONCLUSIONS: Dust exposure to flours may not only cause allergic sensitization but also induce chronic changes in lung function.