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Published on: February 1, 2018
Genotoxic evaluation of occupational exposure to antineoplastic drugs
Andres Felipe Aristizabal-Pachon1, Willian Orlando Castillo2
11Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Carrera 7 # 43-82, Bogota, D.C. Colombia.
Abstract:
During the last years, several reports have provided evidence about adverse health effects on personal involved in Antineoplastic Drugs (ANPD) handling. ANPD has the ability to bind DNA, thus produce genotoxic damage. In this way, XRCC1 and XRCC3 proteins are necessary for efficient DNA repair and polymorphisms in this genes can be associated with an individual response to ANPD exposure. Therefore, the aim of this study was to evaluate genetic damage of occupational exposure to antineoplastic drugs and the possible effect of XRCC1 and XRCC3 polymorphisms in oncology employees from Bogotá, Colombia. Peripheral blood samples were obtained from 80 individuals, among exposed workers and healthy controls. The comet assay and Cytokinesis-block micronucleus cytome assay was performed to determinate genetic damage. From every sample DNA was isolated and genotyping for XRCC1 (Arg194Trp, Arg280His and Arg399Gln) and XRCC3 (Thr241Met) SNPs by PCR-RFLP. The exposed group showed a significant increase of comet assay results and micronucleus frequency, compared with unexposed group. It was observed a gender, exposure time and workplace effect on comet assay results. Our results showed no significant associations of comet assay results and micronucleus frequency with either genotype, allele, nor haplotype of XRCC1 and XRCC3 SNPs. The results suggest that occupational exposure to ANPD may lead to genotoxic damage and even be a risk to human health. To our knowledge, this is the first study to assess the genotoxic damage of occupational exposure to APND in South America.
Insights
Occupational exposure to antineoplastic drugs (ANPD) causes genotoxic damage in oncology workers. Genetic variations in XRCC1 and XRCC3 did not influence this damage, highlighting ANPD risks.
Area of Science:
- Occupational Health
- Genetics
- Toxicology
Background:
- Antineoplastic drugs (ANPD) are associated with adverse health effects due to their DNA-binding and genotoxic potential.
- XRCC1 and XRCC3 proteins are crucial for DNA repair, and their polymorphisms may influence individual responses to ANPD exposure.
Purpose of the Study:
- To evaluate genetic damage in oncology employees occupationally exposed to ANPD in Bogotá, Colombia.
- To investigate the potential effect of XRCC1 and XRCC3 gene polymorphisms on ANPD-induced genotoxicity.
Main Methods:
- Comet assay and Cytokinesis-block micronucleus cytome assay were used to assess genetic damage in 80 peripheral blood samples (exposed workers and controls).
- Genotyping for XRCC1 (Arg194Trp, Arg280His, Arg399Gln) and XRCC3 (Thr241Met) single nucleotide polymorphisms (SNPs) was performed using PCR-RFLP.
Main Results:
- Exposed workers showed significantly higher comet assay results and micronucleus frequency compared to the unexposed group.
- Gender, exposure duration, and workplace were found to influence comet assay outcomes.
- No significant associations were observed between genetic damage markers and XRCC1/XRCC3 genotypes, alleles, or haplotypes.
Conclusions:
- Occupational exposure to ANPD can lead to significant genotoxic damage, posing a potential risk to human health.
- This study is the first in South America to assess the genotoxic effects of occupational ANPD exposure.
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