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      Pollutant effects on genotoxic parameters and tumor-associated protein levels in adults: a cross sectional study

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          Abstract

          Background

          This study intended to investigate whether residence in areas polluted by heavy industry, waste incineration, a high density of traffic and housing or intensive use of pesticides, could contribute to the high incidence of cancer observed in Flanders.

          Methods

          Subjects were 1583 residents aged 50–65 from 9 areas with different types of pollution. Cadmium, lead, p,p'-DDE, hexachlorobenzene, PCBs and dioxin-like activity (Calux test) were measured in blood, and cadmium, t,t'-muconic acid and 1-hydroxypyrene in urine. Effect biomarkers were prostate specific antigen, carcinoembryonic antigen and p53 protein serum levels, number of micronuclei per 1000 binucleated peripheral blood cells, DNA damage (comet assay) in peripheral blood cells and 8-hydroxy-deoxyguanosine in urine. Confounding factors were taken into account.

          Results

          Overall significant differences between areas were found for carcinoembryonic antigen, micronuclei, 8-hydroxy-deoxyguanosine and DNA damage. Compared to a rural area with mainly fruit production, effect biomarkers were often significantly elevated around waste incinerators, in the cities of Antwerp and Ghent, in industrial areas and also in other rural areas. Within an industrial area DNA strand break levels were almost three times higher close to industrial installations than 5 kilometres upwind of the main industrial installations (p < 0.0001). Positive exposure-effect relationships were found for carcinoembryonic antigen (urinary cadmium, t,t'-muconic acid, 1-hydroxypyrene and blood lead), micronuclei (PCB118), DNA damage (PCB118) and 8-hydroxy-deoxyguanosine (t,t'-muconic acid, 1-hydroxypyrene). Also, we found significant associations between values of PSA above the p90 and higher values of urinary cadmium, between values of p53 above the p90 and higher serum levels of p,p'-DDE, hexachlorobenzene and marker PCBs (PCB 138, 153 and 180) and between serum levels of p,p'-DDE above the p90 and higher serum values of carcinoembryonic antigen. Significant associations were also found between effect biomarkers and occupational or lifestyle parameters.

          Conclusion

          Levels of internal exposure, and residence near waste incinerators, in cities, or close to important industries, but not in areas with intensive use of pesticides, showed positive correlations with biomarkers associated with carcinogenesis and thus probably contribute to risk of cancer. In some rural areas, the levels of these biomarkers were not lower than in the rest of Flanders.

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          Most cited references94

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          Circulating concentrations of insulin-like growth factor-I and risk of breast cancer.

          Insulin-like growth factor (IGF)-I, a mitogenic and antiapoptotic peptide, can affect the proliferation of breast epithelial cells, and is thought to have a role in breast cancer. We hypothesised that high circulating IGF-I concentrations would be associated with an increased risk of breast cancer. We carried out a nested case-control study within the prospective Nurses' Health Study cohort. Plasma concentrations of IGF-I and IGF binding protein 3 (IGFBP-3) were measured in blood samples collected in 1989-90. We identified 397 women who had a diagnosis of breast cancer after this date and 620 age-matched controls. IGF-I concentrations were compared by logistic regression with adjustment for other breast-cancer risk factors. There was no association between IGF-I concentrations and breast-cancer risk among the whole study group. In postmenopausal women there was no association between IGF-I concentrations and breast-cancer risk (top vs bottom quintile of IGF-I, relative risk 0.85 [95% CI 0.53-1.39]). The relative risk of breast cancer among premenopausal women by IGF-I concentration (top vs bottom tertile) was 2.33 (1.06-5.16; p for trend 0.08). Among premenopausal women less than 50 years old at the time of blood collection, the relative risk was 4.58 (1.75-12.0; p for trend 0.02). After further adjustment for plasma IGFBP-3 concentrations these relative risks were 2.88 and 7.28, respectively. A positive relation between circulating IGF-I concentration and risk of breast cancer was found among premenopausal but not postmenopausal women. Plasma IGF-I concentrations may be useful in the identification of women at high risk of breast cancer and in the development of risk reduction strategies. Additional larger studies of this association among premenopausal women are needed to provide more precise estimates of effect.
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            The in vitro micronucleus technique.

            M Fenech (2000)
            The study of DNA damage at the chromosome level is an essential part of genetic toxicology because chromosomal mutation is an important event in carcinogenesis. The micronucleus assays have emerged as one of the preferred methods for assessing chromosome damage because they enable both chromosome loss and chromosome breakage to be measured reliably. Because micronuclei can only be expressed in cells that complete nuclear division a special method was developed that identifies such cells by their binucleate appearance when blocked from performing cytokinesis by cytochalasin-B (Cyt-B), a microfilament-assembly inhibitor. The cytokinesis-block micronucleus (CBMN) assay allows better precision because the data obtained are not confounded by altered cell division kinetics caused by cytotoxicity of agents tested or sub-optimal cell culture conditions. The method is now applied to various cell types for population monitoring of genetic damage, screening of chemicals for genotoxic potential and for specific purposes such as the prediction of the radiosensitivity of tumours and the inter-individual variation in radiosensitivity. In its current basic form the CBMN assay can provide, using simple morphological criteria, the following measures of genotoxicity and cytotoxicity: chromosome breakage, chromosome loss, chromosome rearrangement (nucleoplasmic bridges), cell division inhibition, necrosis and apoptosis. The cytosine-arabinoside modification of the CBMN assay allows for measurement of excision repairable lesions. The use of molecular probes enables chromosome loss to be distinguished from chromosome breakage and importantly non-disjunction in non-micronucleated binucleated cells can be efficiently measured. The in vitro CBMN technique, therefore, provides multiple and complementary measures of genotoxicity and cytotoxicity which can be achieved with relative ease within one system. The basic principles and methods (including detailed scoring criteria for all the genotoxicity and cytotoxicity end-points) of the CBMN assay are described and areas for future development identified.
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              8-Hydroxy-2'-deoxyguanosine as a marker of oxidative DNA damage related to occupational and environmental exposures.

              Oxidative DNA damage is considered to play an important role in pathophysiological processes, ageing and cancer. So far major interest has been on measuring 8-hydroxy-2'-deoxyguanosine (8-OHdG), the preferred methods relying on HPLC or GC-mass spectrometry. The high biological relevance of 8-OHdG is due to its ability to induce G-->T transversions, which are among the most frequent somatic mutations found in human cancers. Effects of workplace exposures on the level of white blood cell 8-OHdG or urinary 8-OHdG have been reported with controversial results. Exposures examined include asbestos, azo-dyes, benzene, fine particulate matter (PM(2.5)), glassworks, polycyclic aromatic hydrocarbons (PAHs), rubber manufacturing, silica, metals, styrene, toluene and xylenes. The available data indicate that there is still a lack of well established dose-response relations between occupational or environmental exposures and the induction of 8-OHdG. Smoking has been most consistently identified as a confounder for 8-OHdG, but various occupational studies did not reveal higher levels of 8-OHdG in smokers. Despite the conflicting results, the reported studies show promise for 8-OHdG as a biomarker of oxidative stress associated with chemical exposure. However, there are critical aspects related to the analytical challenge, artifactual production of 8-OHdG, inter- and intra-individual variation, confounding factors and inter-laboratory differences, implying that further work is needed to reach a consensus on the background level of 8-OHdG.
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                Author and article information

                Journal
                Environ Health
                Environmental Health
                BioMed Central
                1476-069X
                2008
                3 June 2008
                : 7
                : 26
                Affiliations
                [1 ]Study Centre for Carcinogenesis and Primary Prevention of Cancer, Department of Radiotherapy, Nuclear Medicine, and Experimental Cancerology, Ghent University Hospital, De Pintelaan 185 3K3, 9000 Ghent, Belgium
                [2 ]Environmental toxicology, Flemish Institute of Technological Research (VITO), Boeretang 200, 2400 Mol, Belgium
                [3 ]Laboratory of Experimental Cancerology, Department of Radiotherapy, Nuclear Medicine, and Experimental Cancerology, Ghent University Hospital, De Pintelaan 185 P7, 9000 Ghent, Ghent, Belgium
                [4 ]Vrije Universiteit Brussel (VUB), Analytical and Environmental Chemistry (ANCH), Pleinlaan 2, 1050 Brussels, Belgium
                [5 ]Provincial Institute of Hygiene, Kronenburgstraat 45, 2000 Antwerp, Belgium
                [6 ]University of Hasselt, University Campus, Building D, 3590 Diepenbeek, Belgium
                [7 ]Ghent University, Department of Public Health, UZ 2 Blok A, De Pintelaan 185, 9000 Ghent, Belgium
                Article
                1476-069X-7-26
                10.1186/1476-069X-7-26
                2442593
                18522717
                c2e24142-2649-48fd-b3cb-e02e5fa5c241
                Copyright © 2008 De Coster et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 February 2008
                : 3 June 2008
                Categories
                Research

                Public health
                Public health

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