Assessment of abnormal DNA repair responses and genotoxic effects in lead exposed workers

Karakaya, Ali Esat; Özçağlı, Eren; Ertaş, Nusret; Şardaş, Semra

doi:10.1002/ajim.20145

Cited by 25 publications

(13 citation statements)

References 26 publications

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“…Pb is an indirectly acting genotoxic metal, present in the environment as a pollutant of, for example, heavy metal mining, traffic waste by leaded fuel and as a food contaminant (e.g., drinking water by use of Pb pipelines). It is classified as carcinogenic by IARC, and (occupational) exposure to Pb has been reported to cause DNA damage as determined by Comet assay (50)(51)(52). In the current study, Pb-induced carcinoembryonic antigen levels were 1.9 and 1.6 times increased in carriers of the BRCA2 N 372 H polymorphism as compared with heterozygous and wild-type individuals, respectively.…”

Section: Discussionsupporting

confidence: 47%

Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

Ketelslegers

Gottschalk

Koppen

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Cancer has been suggested to result from interactions between genetic and environmental factors, and certain subgroups in the general population may be at increased risk because of their relatively higher susceptibility to environmental carcinogens. The current study, part of a large biomonitoring study conducted in Flanders from 2002 to 2006 (The Flanders Environment and Health Survey), aims to determine these susceptible subpopulations based on multiple genotypic differences between individuals. A random selection of 429 adolescents and 361 adults was genotyped for 36 polymorphisms in 23 genes selected because of their known role in carcinogen metabolism, DNA repair, and oxidative stress. In both age groups, relationships between endogenous exposure to organochloride substances (polychlorinated biphenyl, hexachlorobenzene, dichlorodiphenyl dichloroethane), metals (cadmium, lead), and urinary metabolites (1-hydroxypyrene, trans-trans muconic acid) versus genotoxic effects (Comet assay and micronuclei in lymphocytes, and urinary 8-hydroxydeoxyguanosine) were investigated. In addition, in the study among adults, the relationship of these exposures with several tumor markers (prostate-specific antigen, carcinoembryonic antigen, and p53) was tested. The impact of the genotype on established exposure-effect relationships was evaluated. Eight exposure-effect relationships were found, including three novel associations, with an impact of various genotypes, predominantly affecting biotransformation and oxidative stress response. This study shows that at least part of the interindividual differences in relationships between carcinogen exposure and genotoxic effect can be explained by genotypic differences, enabling the identification of more susceptible subgroups for environmental cancer risks. This may be of relevance for environmental health policy setting. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1902 -12)

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Section: Discussionsupporting

confidence: 47%

Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

Ketelslegers

Gottschalk

Koppen

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…This may induce cellular and tissue damages mediated by reactive oxygen species (ROS) by developing oxidative stress [7] and the associated eventsgenotoxic [27], apoptotic effects [8,9,12,29]. Effects of Pb on immune response have been reported by several investigators, but no clear picture emerges from these data regarding the potential immunotoxic effects.…”

Section: Discussionmentioning

confidence: 99%

“…High doses of Pb (occupational long term exposure) may induce over immunoreactivity with allergic and autoimmune reactions. This differential effect of Pb may explain, at least in part, the reported diversity of in vivo effects on immune response [3,6,13,20,22,24,27,28,29,44]. Th2 reactions are driven by IL-4, IL-5, IL-10, and IL-13 and result in an increase in IgE production.…”

Section: Discussionmentioning

confidence: 99%

“…A growing amount of evidence, and our previous experimental studies in vivo on Wistar rat indicate that high level of Pb causes toxic damage to the organs: liver and kidneys, heart, nervous and immune system, whereas even short-term exposure to low lead doses in vivo and in vitro has immunomodulatory effects that might reflect skewness of the immune response [6,17,19,20,22,27,29]. The existing epidemiologic data and data derived from the in vivo and in vitro studies support that the human immune system may be at increased risk following exposure to Pb and other heavy metals [3,8,15,32,37].…”

Section: Introductionmentioning

confidence: 99%

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Novel developmental immunotoxicology for monitoring the risk assessment for human populations from environmental pollution: alternative methods in vitro

Codorean¹,

Tanase²,

Albulescu³

et al. 2009

Environmental Health Risk V

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There is increasing interest in the development and application of biomarkers for the purpose of risk assessment among human populations exposed to adverse environmental agents. This paper reports a way of monitoring the effects of air pollution on human health by using epidemiological data and in vitro immunotoxicological parameters in lead (Pb) environmentally exposed subjects. Epidemiological and human health statistics collected over the past few years indicate a negative impact of pollution resulting in the increase of the incidence of major diseases: it increases the occurrence of pulmonary diseases, asthma attacks, cardiovascular disease, heart attacks, the development of cancer, and mortality by these major diseases. A pilot study on the target subjects living in the highly polluted air (exposed group H. n=86) indicated statistically significant increased values of blood lead level (BLL) compared to subjects living in low or no Pb polluted air (control group C, n=37). Serum and hematological parameter values, some of them significantly different between the two human groups, also confirm the negative effects of air pollution. In an ex vivo study, using peripheral whole blood cultures and multiplexed immunoassay xMAP technology, the cytokine profiles in the exposed and unexposed subjects were tested, Th1 and pro-inflammatory cytokines TNF-α, IL-1β, IL-2, IFN-γ, IL-6, IL-8, and the regulatory Th2 interleukins IL-4, IL-10 were sensitively modulated in environmental exposure. The cytokine profile detection using small samples (500µg/L) of human whole blood is reproducible and can be effectively used as an in vitro biomarker in human epidemiological studies on environmentally exposed people.

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“…It has been modified by using lesion-specific enzymes (endonuclease III [Endo III] and formamidopyrimidine glycosylase [Fpg]) to be a more specific and a reliable marker for oxidative DNA damage (Collins et al, 1993). Besides the intensive use of these cytogenetic biomarkers in occupational settings (Karahalil et al, 1998;Burgaz et al, 2002;Karakaya et al, 2005;Cakmak et al, 2010), clinical studies (Sardas et al, 2001;Karahalil et al, 2005;Kadioglu et al, 2009;Burgaz et al, 2011), and environmental exposures (Rossner et al, 2011), they are also used in healthy population studies to determine background cytogenetic damage levels (Barale et al, 1998).The glutathione S-transferase (GST) gene family, which encodes phase II metabolizing enzymes, has an important role 1 Department of Toxicology, Faculty of Pharmacy, University of Gazi, Ankara, Turkey. …”

mentioning

confidence: 99%

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

Kadıoğlu

Kocabaş

Demircigil

et al. 2012

Genetic Testing and Molecular Biomarkers

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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 ...

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Assessment of abnormal DNA repair responses and genotoxic effects in lead exposed workers

Cited by 25 publications

References 26 publications

Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

Novel developmental immunotoxicology for monitoring the risk assessment for human populations from environmental pollution: alternative methods in vitro

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

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