Assessment of the genotoxicity and cytotoxicity in environmentally exposed human populations to heavy metals using the cytokinesis‐block micronucleus cytome assay

Abstract

The cytokinesis-block micronucleus cytome (CBMN-Cyt) assay was developed as a system for evaluating DNA damage, cytostasis, and cytotoxicity. The aim of the present study was to estimate levels of micronuclei (MNi), nucleoplasmic bridges (NPBs), nuclear buds (NBUDs), cell death (apoptosis/necrosis), nuclear division index, and nuclear division cytotoxicity index values in the peripheral blood lymphocytes of environmentally exposed subjects to heavy metals from five Bosnian regions, characterized by different exposure to heavy metals. The study was performed using CBMN-Cyt assay, considering factors, such as age, gender and smoking habits and their possible effects on analyzed parameters. In total, 104 healthy subjects were selected (49.04% females and 50.96% males; average age, 35.41 years; 51.92% smokers and 48.08% nonsmokers). There was significant difference between the frequency of NBUDs in Tuzla as compared to the control group. Furthermore, there was observed a statistically significant difference for the frequency of NPBs between Zenica, Olovo, and Kakanj when compared with the controls. Males showed a significantly higher number of apoptotic cells than females in controls. There were significant differences between smokers and nonsmokers in the frequency of NPBs in controls (higher in nonsmokers) and necrotic cells in Olovo (higher in nonsmokers). The pack years of smoking significantly influenced the number of necrotic cells in controls and the frequency of NBUDs in the overall sample. The results of the present study provide evidence of significantly increased frequency of NPBs and NBUDs in exposed subjects, suggesting that these endpoints are highly sensitive markers for measuring genotoxicity.

Multi-centre technical evaluation of the radiation-induced lymphocyte apoptosis assay as a predictive test for radiotherapy toxicity

“…There was no observable effect of patient smoking habit on lymphocyte apoptosis at 0 Gy in our data, suggesting smoking has an interactive rather than a direct effect with radiation. This observation helps explain the apparent contradiction with published laboratory studies on the effect of smoking on lymphocyte apoptosis [27], [28], [29]. The observation of reduced radiation-induced apoptosis in smokers does however concord with the hypothesis that low apoptosis is associated with increased radiation toxicity, because smoking has been identified as a risk factor for toxicity by published clinical studies in a range of cancer types [30], [31], [32], [33], [34].…”

Genotoxicity in Patients on Long-term Proton Pump Inhibitor Therapy in Korea: A Nested Case-control, Prospective, Pilot Study

“…Abnormal levels of MNi, NPBs, and Nbuds in PBLs were indicative of genetic instability. Age, 11,18 gender, 18 smoking status, 18,19 vitamin status, 19 seasonal variations, 15 lifestyle factors, 15,18,20 drugs and transition metals, 21 and occupational and environmental exposure to genotoxic substances 11,22 has been associated with an increased risk of genotoxicity. Also, a variety of diseases, 11,[22][23][24] including Down syndrome, congenital anomalies, aplastic anemia, and solid cancers (e.g., breast cancers) has been associated with genomic instability.…”

The use of genotoxicity biomarkers in molecular epidemiology: applications in environmental, occupational and dietary studies

“…However this paper will cover just the effects in humans and human cells. Table 1 summarizes some studies regarding to environmental exposure, namely air pollutants [67]–[69], heavy metals [70],[71], herbicides [72], mobile radiation [73], pesticides [74],[75], pollution mixture [76], PAHs [77],[78], and pyrethroids [79].…”