Chromosomal damage and polymorphisms of DNA repair genes XRCC1 and XRCC3 in workers exposed to cytostatics.
OBJECTIVES: Medical workers in oncological units have chronically been exposed to low doses of cytostatics (C) with potential consequences on DNA and chromosomal integrity. Our study addresses relationships between chromosomal aberrations (CAs), chromosome (CSA), and chromatid (CTA) types and polymorphisms in DNA repair genes XRCC1 and XRCC3.
METHODS: The study was conducted on 72 exposed individuals from hospitals in Martin (HMT; 28 individuals), Ruzomberok (HRK; 31 medical workers) and in Trstená (HTS; 13 individuals), and on 34 unexposed individuals. Conventional cytogenetic analysis was employed for the detection of CAs. XRCC1 and XRCC3 polymorphisms were assayed for by Taqman SNP genotyping assays ("Assay-by-Demand") using Real-Time allelic discrimination on AB 7 500 equipment (all from Applied Biosystems, Foster City, USA).
RESULTS: Higher frequencies of CAs were detected in exposed individuals than in controls (1.78% versus 1.32%, respectively). The frequency of aberrant cells (Ab.c.) was highest among workers from HRK (1.97%), followed by those from HMT and HTS (1.54% and 1.85 %, respectively). In the exposed group a moderately higher frequency of CTA (0.93%) in comparison with CSA (0.85%) was detected. Higher CAs were detected in individuals with homozygous variant polymorphism in XRCC1 exon 10 gene than in those with wild-type genotype (1.87% versus 1.60%). Variant T allele in XRCC3 exon 7 was also associated with higher CAs (1.71% and 1.74%) as compared to the wild-type C allele (1.45%).
CONCLUSIONS: The detection of individuals with increased susceptibility to genotoxic agents enables to take preventive measures during the working process....