Jodel Alves

Investigation of potential biomarkers for the early diagnosis of cellular stability after the exposure of agricultural workers to pesticides

Agricultural workers involved in the harvest of tobacco crops are regularly exposed to large quantities of pesticides. In order to determine how this exposure to pesticides induces genetic alterations in these workers, blood samples were obtained from 77 exposed individuals, as well as from 60 unexposed subjects. DNA damage was analyzed by the Comet assay and by the micronucleus (MN) test. The antioxidant profile was evaluated by activity of superoxide dismutase (SOD), and the polymorphism of gene PON1 was used as a susceptibility biomarker. The content of inorganic elements in the blood samples was determined by PIXE analysis. Our results demonstrated that the damage frequency, damage index, the MN frequency, and the SOD activity were significantly elevated in the exposed relative to the unexposed group. A modulation of the MN results for the PON1 gene was observed in the exposed group. The concentrations of inorganic elements in the exposed group were higher compared to those of the unexposed group. In this study, we observed that genetic damage, and change in oxidative balance were induced by the exposure of workers to complex mixtures of pesticides in the presence of inorganic compounds, whereby an influence of the genotype was evident.

An Evaluation of Occupational Exposures to Pesticides in Brazil

All over the world, pesticides are frequently used in large quantities. Even though these substances are potentially toxic and may affect the human health, depending on the degree of exposure, contamination, and toxicity, they are nevertheless constantly released into the environment. Currently, predominantly organophosphorus (OP) and carbamate (CBM) pesticides, which are considered neurotoxic due to their potential to inhibit cholinesterase (ChE) activity, are used frequently in developing countries. Accordingly, many intoxication symptoms regarding these chemicals are diagnosed via the ChE analysis and its degree of inhibition. This is therefore the method of choice for biomonitoring exposed individuals, and has been described in the evaluation of thirteen Brazilian studies, which we retrieved from different online databases and present in this review. However, conflicting results on the effects on ChE as a result of repeated and prolonged exposure to low doses still prevail, mainly because farmers are usually exposed to mixtures of pesticides simultaneously. Reviews based exclusively on the laboratory analyses of ChE activity render the clinical interpretation difficult, as it is not a very sensitive method and does not efficiently address the reality of chronic intoxications in the absence of clinical signs. Many diseases among farmers are related to genetic damage, which includes carcinogenic and neurotoxic processes, reproductive and developmental defects, hormonal changes, as well as immune and neurodegenerative diseases. In this article, we therefore discuss the use of different biomarkers for the occupational evaluation, as clinical interpretations still require improvement and widely available laboratory tests still remain unattainable, especially with respect to individual conditions arising from mild to moderate exposures, which might have no immediate, but can have significant detrimental long-term health effects on the health of exposed individuals.

Role of PON1, SOD2, OGG1, XRCC1, and XRCC4 polymorphisms on modulation of DNA damage in workers occupationally exposed to pesticides

Tobacco farming has been proving to induce poor health outcomes in agricultural workers, genomic instability being the triggering one. This study evaluated influence of PON1 (paraoxonase 1), SOD2 (superoxide dismutase), OGG1 (8-oxoguanine glycosylase), XRCC1 (X-ray repair cross-complementing protein 1), and XRCC4 (X-ray repair cross-complementing protein 4) genes polymorphisms on DNA damage in 121 subjects occupationally exposed to pesticides mixtures and nicotine at tobacco fields and 121 non-exposed individuals. Inorganic elements (Cl, P, S and Zn) and cotinine levels were found increased in farmers, confirming exposure. Results show higher frequencies of buccal micronucleus (MN), nuclear buds (NBUD), binucleated cells (BN) and damage index (comet assay), reduced telomere length (TL), and increased parameters of oxidative stress in farmers compared to non-exposed individuals. PON1 Gln/Gln genotype was associated with increased MN frequency. SOD2 Val/Val showed association with increased frequency of MN and NBUD and decreased antioxidant activity. The XRCC1 Arg/Arg showed protective effect for MN, BN and TL, which was also positively influenced by OGG1 -/Cys. MN was decreased in XRCC4 -/Ile farmers. These genotypes also showed a risk for antioxidant activity. Our study proposes that PON1 and SOD2 variants play a role in xenobiotic-metabolizing system in farmers, while base excision repair (BER) pathway could be the repair mechanism involved in genomic instability suffered by tobacco farmers.