title: Measurement of DNA repair deficiency in workers exposed to benzene.
abstract: We hypothesize that chronic exposure to environmental toxicants can induce genetic damage causing DNA repair deficiencies and leading to the postulated mutator phenotype of carcinogenesis. To test our hypothesis, a host cell reactivation (HCR) assay was used in which pCMVcat plasmids were damaged with UV light (175, 350 J/m2 UV light), inactivating the chloramphenicol acetyltransferase reporter gene, and then transfected into lymphocytes. Transfected lymphocytes were therefore challenged to repair the damaged plasmids, reactivating the reporter gene. Xeroderma pigmentosum (XP) and Gaucher cell lines were used as positive and negative controls for the HCR assay. The Gaucher cell line repaired normally but XP cell lines demonstrated lower repair activity. Additionally, the repair activity of the XP heterozygous cell line showed intermediate repair compared to the homozygous XP and Gaucher cells. We used HCR to measure the effects of benzene exposure on 12 exposed and 8 nonexposed workers from a local benzene plant. Plasmids 175 J/m2 and 350 J/m2 were repaired with a mean frequency of 66% and 58%, respectively, in control workers compared to 71% and 62% in exposed workers. Conversely, more of the exposed workers were grouped into the reduced repair category than controls. These differences in repair capacity between exposed and control workers were, however, not statistically significant. The lack of significant differences between the exposed and control groups may be due to extremely low exposure to benzene (< 0.3 ppm), small population size, or a lack of benzene genotoxicity at these concentrations. These results are consistent with a parallel hprt gene mutation assay.
authors.affiliation: Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555-1110, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Hallberg
authors.forename: R
authors.initials: R
authors.lastname: el Zein
authors.forename: L
authors.initials: L
authors.lastname: Grossman
authors.forename: W W
authors.initials: WW
authors.lastname: Au
mesh_terms: D000328:Adult; D001554:Benzene / Q000009:adverse effects*; D002460:Cell Line; D002617:Chemical Industry; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D010957:Plasmids / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D015500:Chloramphenicol O-Acetyltransferase; D001554:Benzene