t(14; 18) Translocations in Dioxin-Exposed Workers [2013]

Details

• Personal Author:
  Dardynskaia I ; Hryhorczuk D
• Description:
  Occupational exposure to dioxins has been associated with increased risk of Non-Hodgkin's lymphoma in previous epidemiologic studies. Environmental exposure to 2,3,7,8-TCDD following the Seveso accident has been associated with increased frequency of t(14;18) translocations, which is a critical step in the carcinogenesis pathway for follicular lymphoma. We investigated the association between dioxin exposure and the prevalence and frequency of t(14;18) translocations in 218 former workers of a chemical plant that produced chlorinated phenols and chlorphenoxy acids and 150 general population controls from an unexposed city, who were frequency matched to the exposed on age, gender, and ethnicity. The exposed had a mean blood 2,3,7,8 - TCDD level of 51.02 lipid-adjusted ppt (median 22.9) vs 2.75 (median 2.30) for controls, and a mean TEQ of 109.71 (median 62.38) vs 20.83 (median 17.20) for the unexposed. We did not observe an increase in the prevalence or frequency of t(14;18) translocations between the exposed and unexposed. We did, however, observe a significant increase in the frequency of t(14;18) translocations with increasing blood dioxin levels in the subset of workers who had current or past chloracne. We also investigated gene expression in a random sample of 60 exposed and 30 unexposed. Dioxin exposure, as measured by blood levels, was associated with statistically significant effects on gene expression in peripheral blood mononuclear cells in multiple candidate genes and pathways. In the AhR pathway, dioxin exposure was associated with significant up-regulation of AHR, ARNT, NRIP1, TIPARP, and TRIP11 while HSP90AA1 was significantly down-regulated. In the Anti-Apoptosis pathway, BAX, BCL2AI and BCL2L1 were significantly down-regulated while PTGS2 was significantly up-regulated. Dioxin exposure affected multiple genes in the inflammation pathway. IL8, PARP1, SEPINB2, NFKB1, and STAT3 were significantly up-regulated while IL17RB was significantly down-regulated. In addition, TNF and BACH2 were borderline up-regulated while CCL2 was borderline down-regulated. In the lipid metabolism pathway, MTMR7, GRN, and ALOX15B were significantly up-regulated, while ST8SIAI was borderline down-regulated. In the cell cycle and translation pathways, RB1 and CTBP2 were significantly up-regulated while PTN and EIF2S1 were significantly down-regulated. In the WNT signaling pathway, CTNNB1 was significantly up-regulated while WNT5A was borderline down-regulated. Among the other candidate genes, dioxin exposure was associated with significant up-regulation of TP53, PRDM1, NFIL3, and BTN1A1, significant down-regulation of HIST1H2BE and CDEBPD, and borderline up-regulation of ALDH3A2. This study provides important data on the molecular effects of dioxin on candidate genes and pathways. This study also suggests that there are important differences in susceptibility to the effects of dioxin in humans. This susceptibility is likely mediated through genetic or epigenetic mechanisms. Susceptibility to chloracne appears to provide a promising avenue for further investigation into the role of gene-environmental interactions in modulating dioxin toxicity. [Description provided by NIOSH]
• Subjects:
  Dioxins Genetics Manufacturing And Industrial Facilities Neoplasms Occupational Exposure Occupational Health Safety
• Keywords:
  Cell Signaling Chemical Industry Workers Gene Expression Gene Regulation Genes Lymphatic Cancer Occupational Exposure
• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Final Grant Report
• Place as Subject:
  Illinois ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-74
• NIOSHTIC Number:
  nn:20056793
• NTIS Accession Number:
  PB2019-101415
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R01-OH-008976, 2013 Dec; :1-74
• Contact Point Address:
  Daniel Hryhorczuk, MD, MPH, Center for Global Health, University of Illinois College of Medicine, 1940 W. Taylor Street, 2nd Floor, Chicago, Illinois 60612
• Email:
  dhryhorc@uic.edu
• CAS Registry Number:
  2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS RN 1746-01-6)
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Illinois at Chicago
• Peer Reviewed:
  False
• Start Date:
  20080801
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20130731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0a9a0c4d499e122da66f414015f9523d0c2d984b05af827d6a14c0974d0ee92e678a76d32c101759a65b304ad252d86cc6912f44c2f9f48373d2ab0d900d385a
• Download URL:
  https://stacks.cdc.gov/view/cdc/218912/cdc_218912_DS1.pdf
• File Type:
  [PDF - 3.16 MB ]