Evaluation of genome damage in subjects occupationally exposed to possible carcinogens
Davor Zeljezic1, Marin Mladinic2, Nevenka Kopjar1
1Division for Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Abstract:
In occupational exposures, populations are simultaneously exposed to a mixture of chemicals. We aimed to evaluate DNA damage due to possible carcinogen exposure (phenylhydrazine, ethylene oxide, dichloromethane, and 1,2-dichloroethane) in lymphocytes of pharmaceutical industry workers from the same production line. Population comprised 16 subjects (9 females and 7 males) who were exposed to multiple chemicals for 8 months. Genome damage was assessed using alkaline comet assay, micronucleus assay, and comet assay coupled with fluorescent in situ hybridization (comet-FISH). After 8 months of exposure, the issue of irregular use of all available personal protective equipment (PPE) came into light. To decrease the risk of exposure, strict use of PPE was enforced. After 8 months of strict PPE use, micronuclei frequency and comet assay parameters in lymphocytes of pharmaceutical workers significantly decreased compared with prior period of irregular PPE use. Comet-FISH results indicated a significant shift in distribution of signals for the TP 53 gene toward a more frequent occurrence in the comet tail. Prolonged exposure to possible carcinogens may hinder DNA repair mechanisms and affect structural integrity of TP 53 Two indicators of loss of TP 53 gene integrity have risen, namely, TP 53 fragmentation rate in lymphocytes with persistently elevated primary damage and incidence of TP 53 deletions in undamaged lymphocytes.
Insights
Strict use of personal protective equipment (PPE) significantly reduced DNA damage in pharmaceutical workers exposed to carcinogens. This highlights the importance of PPE in mitigating occupational health risks and protecting genomic integrity.
Area of Science:
- Occupational Health
- Genotoxicology
- Industrial Hygiene
Background:
- Workers in the pharmaceutical industry face simultaneous exposure to multiple chemicals.
- Assessing DNA damage from occupational carcinogen exposure is crucial for worker safety.
Purpose of the Study:
- To evaluate DNA damage in pharmaceutical workers exposed to a mixture of possible carcinogens.
- To investigate the impact of personal protective equipment (PPE) use on genotoxicity.
Main Methods:
- Alkaline comet assay, micronucleus assay, and comet assay coupled with fluorescent in situ hybridization (comet-FISH) were used.
- Lymphocytes from 16 pharmaceutical workers were analyzed before and after strict PPE enforcement.
Main Results:
- Micronuclei frequency and comet assay parameters significantly decreased after strict PPE use.
- Comet-FISH revealed a shift in TP53 gene distribution, indicating fragmentation and deletions.
- TP53 gene integrity loss indicators increased with prolonged exposure.
Conclusions:
- Strict adherence to PPE significantly reduces occupational DNA damage.
- Prolonged exposure to carcinogens may impair DNA repair and TP53 gene integrity.
- Monitoring genotoxicity and enforcing PPE are vital in the pharmaceutical industry.
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