Mutation Research/Genetic Toxicology and Environmental Mutagenesis
Cytogenetic effects of hexavalent chromium in Bulgarian chromium platers
Introduction
Hexavalent chromium (Cr(VI)) is an established mutagen as well as human carcinogen of the respiratory system, particularly lung carcinogen [1], [2]. The carcinogenic action of some chromium compounds has been demonstrated in laboratory animals, too [3], [4]. Soluble Cr(VI) compounds have a corrosive action to skin and mucous membranes, especially to the nasal septum [3]. Inhaled aerosols of Cr(VI) are readily absorbed from the respiratory tract. In addition, some chromium compounds are found to be nephrotoxic, as well as allergenic [5], [6].
It is considered that genotoxic and carcinogenic activity of Cr(VI) is connected with its metabolism in the cell. Unlike trivalent chromium (Cr(III)), Cr(VI) penetrates easily the cell membrane, and is rapidly taken up by the cell. Intracellularly, Cr(VI) undergoes a complicated cascade of reductive metabolic processes, probably involving redox systems of ascorbate, glutathione or cysteine, etc. Passing through Cr(V) and Cr(IV), it is converted to Cr(III) which is stable. The latter reacts with several cellular constituents including nucleic acids and induces different types of DNA damage such as CAs, DNA strand breaks [5], [6], DNA–protein cross links, as well as homologous and non-homologous somatic recombination [3], [7], [8], [9].
In order to prove the relationship between exposure and cancer risk and to define safe levels of Cr(VI) exposure under occupational conditions, biological monitoring of exposed workers is of main importance. It should include estimations of external and internal exposure as well as studies of early biological effects, e.g. DNA damage, considered as early stages of carcinogenesis. The external exposure is measured by the concentration of Cr(VI) in the air at the working places. The internal exposure should be determined by analyses of body fluids, for example chromium content in urine. Early effects in carcinogenesis are genetic alterations such as chromosome aberrations (CAs), sister chromatid exchanges (SCEs), gene mutations, etc. [10]. The monitoring of these biomarkers is routinely carried out in blood lymphocytes. However, the existing data on the in vivo cytogenetic effects of Cr(VI) as studied on human blood cells are rather contradictory [11], [12], [13], [14] if opposed to the numerous papers reporting its genotoxicity if other end-points are investigated [1], [3], [7]. Whether peripheral blood lymphocytes (PBLs) are suitable for investigations of chromium genotoxic effects under occupational conditions, it is still a matter of dispute. Cr(VI) is known to cause cancer of the respiratory system, particularly lung cancer. Toxicokinetic studies of inhaled Cr(VI) have shown that only a small fraction of the total dose is distributed in the body while the bulk of Cr(VI) is deposited in the lungs where it remains for a very long time [15]. Therefore, it might be supposed that alternative cell test systems should be developed for or adapted to the purposes of human biomonitoring.
In this study the utility of peripheral lymphocytes as well as of buccal cells as target cells for genotoxic effects resulting from exposure to Cr(VI) has been investigated in a cohort of Bulgarian chromium platers.
Section snippets
The investigated cohort
For the chromium platers in Yambol, Bulgaria, relevant data on occupational history, health status, smoking habits, recent X-ray diagnostic examinations were collected by personal interviews and filled-up questionnaires (Table 1). All workers have reported regular use of personal protection devices like disposable masks, gloves, etc. Special interest was paid to perforation of the nasal septum due to chronic exposure by inhalation of chromium compounds. The identification of the exposed workers
CAs and SCEs
No differences were found between the study groups for the frequencies of CAs (1.38±0.20% in the exposed group versus 1.28±0.22% in the control workers, see Table 3) as well as SCEs/cell (7.07±0.21 in the workers versus 6.52±0.37 in the controls) as scored in the peripheral lymphocytes. Single dicentrics and minutes were found in individuals belonging to both study groups who were subjected to medical diagnostic X-ray examinations during the year preceding sampling. The frequency of CAs in both
Discussion
A bulk of evidence has been accumulated of the carcinogenic activity of Cr(VI) [1], [2], [4], [22]. Many authors have reported that Cr(VI) compounds show a genotoxic effects [3], [7], [13], [22]. Nevertheless, the mechanism of its action is not clarified and, on the basis of the contemporary knowledge, it is assumed to be a complex one [22], [23], [24].
In the present study a significant increase is found in the frequencies of MN in PBLs as well as in buccal mucosa cells of chromium platers as
Acknowledgements
This study has been supported by grants from EU INCO-Copernicus Project no. IC15CT960302 and by the National Swedish Environment Protection Agency.
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2022, Biomedicine and PharmacotherapyCitation Excerpt :Study on Chromium platers of Yambol, Bulgaria Cr-exposed (more than 0.05 mg/m3) workers' peripheral lymphocytes contained an increased number of micronuclei (MNs). As a result of the Cr (VI)-toxicity, clastogenic and aneugenic effects were observed [104]. An investigation of Cr-workers in Taiwan's electroplating plants (exposure group involving 35 workers and an exposure range between 0.049 −1.130 mg/m3) reported sister chromatid exchange and cytogenetic damage [105].
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2018, Comprehensive Toxicology: Third EditionBiomonitoring of humans exposed to arsenic, chromium, nickel, vanadium, and complex mixtures of metals by using the micronucleus test in lymphocytes
2016, Mutation Research - Reviews in Mutation ResearchCytotoxic and genotoxic potential of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA complex in human hepatoma (HepG2) cells
2016, ChemosphereCitation Excerpt :And lastly, the formed Cr(III) binds to cellular macromolecules including DNA, creating stable Cr(III)-DNA adducts, DNA-Cr-DNA crosslinks, protein-Cr-DNA crosslinks (Zhitkovich, 2011) as well as single (Ueno et al., 2001) and double DNA strand breaks (Ha et al., 2004) that lead to mutations and chromosomal breaks (Zhitkovich, 2011). The genotoxicity of Cr(VI) is well reported and has been demonstrated in vitro (for review see Nickens et al. (2010)), in plants (Rodriguez et al., 2011), in test animals in vivo (Ahmed et al., 2013; Bigorgne et al., 2010; Dana Devi et al., 2001; Kumar et al., 2013; Manerikar et al., 2008) and in occupationally exposed workers [for review see Benova et al. (2002), Li et al. (2014) and Proctor et al. (2014)]. Cr(VI) induced damage can lead to dysfunctional DNA replication and transcription, dysregulated DNA repair mechanisms, aberrant cell cycle checkpoints, microsatellite and genomic instability, epigenetic modifications, which all play an important role in Cr(VI) induced carcinogenesis (Nickens et al., 2010).
Assessment of the mode of action for hexavalent chromium-induced lung cancer following inhalation exposures
2014, ToxicologyCitation Excerpt :The MN frequency in nasal mucosa was not altered in chromium platers, whereas a significant increase (p < 0.01) in MN was found in 2 of 3 subjects involved in accidental ethylene oxide leakage, and a non-significant increase in MN was found in the group chronically exposed to ethylene oxide. Airborne concentrations of Cr(VI) were not reported in Sarto et al. (1990) and Benova et al. (2002). In Vaglenov et al. (1999), the mean total chromium concentrations were reported to be 43 and 83 μg/m3 in low- and high-exposure groups.