title: Evaluation of genome damage in subjects occupationally exposed to possible carcinogens.
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.
authors: Division for Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
authors: Davor
authors: D
authors: Zeljezic
authors: Division for Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia mmladinic@imi.hr.
authors: Marin
authors: M
authors: Mladinic
authors: Division for Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
authors: Nevenka
authors: N
authors: Kopjar
authors: Occupational Health Practice, Zagreb, Croatia.
authors: Azra Hursidic
authors: AH
authors: Radulovic
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D043171:Chromosomal Instability; D020552:Comet Assay; D017523:Croatia / Q000453:epidemiology; D004249:DNA Damage; D004345:Drug Industry; D005260:Female; D015894:Genome, Human / Q000187:drug effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control; D009784:Occupational Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control; D016273:Occupational Exposure / Q000009:adverse effects* / Q000517:prevention & control; D000067393:Personal Protective Equipment; D012306:Risk; D016159:Tumor Suppressor Protein p53 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000078329:Workforce
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D009153:Mutagens; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Comet assay; TP 53; comet-FISH; micronucleus assay; occupational exposure