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.

Lung cancer is the leading cause of all cancer-related deaths in the US. The need to develop more accurate cancer risk assessment tools is imperative to improve the ability to identify individuals at greatest risk of developing disease. The Cytokinesis-Blocked Micronucleus Cytome Assay (CBMNcyt) presents a sensitive and specific method of assessing DNA damage. We have previously reported that this assay is sensitive to genetic damage caused by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and that binucleated cells with micronuclei, nucleoplasmic bridges and nuclear buds are strong predictors of lung cancer risk. The current study confirmed our previous findings and sought to identify the specific chromosomes involved in lung carcinogenesis. Spectral karyotyping was conducted on a subset of lung cancer cases [n = 116] and cancer-free controls [n = 126] with the highest CBMNcyt endpoints, on baseline and NNK-treated blood lymphocytes. After adjusting for age, gender, race/ethnicity, smoking status, and pack and smoke years, consistent significant associations between chromosome: 9, 19, 22, X, at baseline; chromosome: 3, 4, and 16 after NNK-induction; and chromosome: 1, 13, and 17 at both baseline and NNK-induction; and lung cancer risk (all P ≤ 0.05) were observed. Several of these chromosomes harbor critical genes involved in lung carcinogenesis, such as the FHIT gene, CDKN2A, PADPRP, and TP53. Our results indicate that the CBMNcyt assay when used in conjunction with other cytogenetic methodologies can increase our ability to identify specific chromosomal regions associated with DNA damage, thereby improving our understanding of the underlying mechanisms involved in individual cancer predisposition.

BACKGROUND: Although tobacco exposure is the predominant risk factor for lung cancer, other environmental agents are established lung carcinogens. Measuring the genotoxic effect of environmental exposures remains equivocal, as increases in morbidity and mortality may be attributed to coexposures such as smoking.
METHODS: We evaluated genetic instability and risk of lung cancer associated with exposure to environmental agents (e.g., exhaust) and smoking among 500 lung cancer cases and 500 controls using the cytokinesis-blocked micronucleus (CBMN) assay. Linear regression was applied to estimate the adjusted means of the CBMN endpoints (micronuclei and nucleoplasmic bridges). Logistic regression analyses were used to estimate lung cancer risk and to control for potential confounding by age, gender, and smoking.
RESULTS: Cases showed significantly higher levels of micronuclei and nucleoplasmic bridges as compared with controls (mean ± SEM = 3.54 ± 0.04 vs. 1.81 ± 0.04 and mean ± SEM = 4.26 ± 0.03 vs. 0.99 ± 0.03, respectively; P < 0.001) with no differences among participants with or without reported environmental exposure. No differences were observed when stratified by smoking or environmental exposure among cases or controls. A difference in lung cancer risk was observed between nonexposed male and female heavy smokers, although it was not statistically significant (I(2) = 64.9%; P value for Q statistic = 0.09).
CONCLUSIONS: Our study confirms that the CBMN assay is an accurate predictor of lung cancer and supports the premise that heavy smoking may have an effect on DNA repair capacity and in turn modulate the risk of lung cancer.
CONCLUSIONS: Identifying factors that increase lung cancer risk may lead to more effective prevention measures.

Formaldehyde, classified by the IARC as carcinogenic in humans and experimental animals, is a chemical agent that is widely used in histopathology laboratories. The exposure to this substance is epidemiologically linked to cancer and to nuclear changes detected by the cytokinesis-block micronucleus test (CBMN). This method is extensively used in molecular epidemiology, since it provides information on several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomere fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA. The aim of this study is to compare the frequency of genotoxicity biomarkers, provided by the CBMN assay in peripheral lymphocytes and the MN test in buccal cells, between individuals occupationally exposed and non-exposed to formaldehyde and other environmental factors, namely tobacco and alcohol consumption. The sample comprised two groups: 56 individuals occupationally exposed to formaldehyde (cases) and 85 unexposed individuals (controls), from whom both peripheral blood and exfoliated epithelial cells of the oral mucosa were collected in order to measure the genetic endpoints proposed in this study. The mean level of TWA(8h) was 0.16±0.11 ppm (

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