Assessment of Individual Susceptibility to Baseline DNA and Cytogenetic Damage in a Healthy Turkish Population: Evaluation with Lifestyle Factors

Abstract

Background: Cytogenetic biomarkers are most frequently used well-established endpoints in human population studies with their sensitivity for measuring exposure to genotoxic agents. They have an important role as early predictors of cancer risk. Identification of individual genotypes of metabolic gene polymorphisms helps to understand the modulation of cancer susceptibility by environmental exposures, such as cigarette smoking and other lifestyle factors. Aim: To evaluate individual susceptibility to chemicals, we determined individual DNA damage related to glutathione S-transferase (GST) genotypes (GSTM1, GSTT1, and GSTP1) in a Turkish population. Methods: Peripheral blood lymphocytes (PBL) and DNA samples of 127 subjects were analyzed for the presence of DNA damage, using single-cell gel electrophoresis (the Comet assay), and for cytogenetic parameters (chromosomal aberrations [CAs], bleomycin-induced CA, and a cytokinesis-blocked micronucleus assay), and the polymerase chain reaction/restriction fragment length polymorphism method, respectively. Results: Individuals carrying a GSTT1-null allele showed higher frequencies of CA and micronucleus (MN) ( p = 0.026, p = 0.003, respectively), whereas the GSTM1-null and GSTP1 mutant genotypes did not show any differences in cytogenetic parameters. Our findings demonstrated that none of the lifestyle factors (smoking, alcohol drinking, dietary habits, vitamin intake, and physical activity), except for vitamin intake ( p = 0.002), were significantly associated with the studied cytogenetic parameters. Conclusion: Our results suggest that the GSTT1 gene polymorphism may influence the baseline cytogenetic frequency in a healthy population. IntroductionT he role of genetic factors (early predictors) in determining human susceptibility to the carcinogenic effects of chemical agents has become a major research area in molecular epidemiology (Au, 2007). Biomarkers of early biologic effect include cytogenetic assays, such as chromosomal aberrations (CAs), micronucleus (MN), and the comet assay, which are the most frequently used endpoints in human population studies. Their sensitivity for measuring exposure to genotoxic agents and their role as early predictors of cancer risk have contributed to this success (Bonassi et al., 2005). CAs and cytokinesis-blocked micronucleus assay (CBMN) have value as biological dosimeters, and more recently, as predictors of cancer risk in epidemiological studies (Bonassi et al., 2004(Bonassi et al., , 2011. Mechanistic evidence linking CAs to early stages of cancer has been supported by the results of cohort studies that associated the CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence (Bonassi et al., 2008). Furthermore, it has been found that an increased MN frequency in peripheral blood lymphocytes predicts the risk of cancer in humans (Bonassi et al., 2007). The alkaline comet assay is also one of the most promising biomarkers to detect single-strand breaks (SSBs) as well as alkaline-labile sites under ...

Application of the comet assay in human biomonitoring: An hCOMET perspective

“…The effect of regular exercise on the basal level of DNA damage in volunteers who exercise regularly has also been tested. While some authors report a lower level of DNA damage in lymphocytes of people who perform regular exercise [19,[120][121][122], others did not find any association between exercise and the level of DNA damage [37,123] and some even report a higher level [124]. In this last study, even the H 2 O 2 resistance was lower in sportsmen doing regular exercise, namely rugby players.…”

The role of oxidative DNA damage and GSTM1, GSTT1, and hOGG1 gene polymorphisms in coronary artery disease risk

“…The basic alkaline technique was followed, with modifications for the detection of oxidized bases using bacterial repair endonucleases, as previously described ( 16 ). Before electrophoresis, the lymphocytes were treated with either buffer to examine basal DNA damage or Endo III or Fpg to examine pyrimidine or purine base damage, respectively.…”

GSTM1, GSTP1, and GSTT1 genetic variability in Turkish and worldwide populations

“…As such, reference genetic data for the Turkish population are absolutely mandatory for assessing the reliability of genetic association studies conducted with this population. Several studies of different health‐related traits in Turkish individuals have been performed to assess the role of GSTM1 , GSTT1 , and GSTP1 gene variants in disease etiology, including ones focusing on respiratory diseases (Calikoglu et al, ), diabetes (Gonul et al, ), chromosomal aberrations (Kadioglu et al, ), cancers (Altayli et al, ; Berber et al, ), and cardiovascular diseases (Taspinar et al, ). Furthermore, the genetic investigation of disease‐associated loci in human populations with a complex demography history, such as the Turkish population, furnishes a valuable opportunity to investigate the genetic relationship between human history and genetic predispositions to common diseases.…”