Stilbene Estrogen Produces Higher Levels of Mitochondrial DNA Adducts than Nuclear DNA Adducts in the Target Organ of Cancer (Liver) of Male Sprague Dawley Rats

Details

• Personal Author:
  Roy D ; Thomas RD
• Description:
  We have previously demonstrated that diethylstilbestrol is metabolized to diethylstilbestrol reactive metabolites by mitochondrial enzymes in vitro. In vitro, these reactive intermediates bind to mitochondrial DNA. Here we have investigated the in vivo formation of diethylstilbestrol adducts with mitochondrial DNA and the nature of mitochondrial DNA-diethylstilbestrol adducts. Diethylstilbestrol exposure to male rats produced several adducts in mitochondrial DNA of both kidney and liver. The total relative adduct levels were 7-fold higher in mitochondrial DNA than in nuclear DNA in the target organ of cancer (liver) of Sprague Dawley rats. The chromatographic mobility of mitochondrial DNA adducts formed in vivo were similar to that of dGMP-DES quinone adducts formed in vitro. These findings suggest that mitochondrial DNA appears more susceptible to formation of diethylstilbestrol adducts than nuclear DNA, and the results suggest that obstruction of replication and/or transcription of the mitochondrial genes by covalent modifications of the mitochondrial DNA by diethylstilbestrol may produce mitochondrial genomic instability in vivo and may provide an explanation for the carcinogenic effects of DES. [Description provided by NIOSH]
• Subjects:
  Animals Carcinogens Endocrine System Estrogens Occupational Health Safety
• Keywords:
  Animal Studies Cellular Effects DNA Adducts Endocrine Disruptors Estrogenic Hormones In Vivo Studies
• ISSN:
  1021-335X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Alabama ; Florida ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  8
• Issue:
  5
• NIOSHTIC Number:
  nn:20057624
• Citation:
  Oncol Rep 2001 Sep; 8(5):1035-1038
• Contact Point Address:
  Dr Ronald D. Thomas, College of Pharmacy, Florida A & M University, Tallahassee, FL-32307, USA
• Email:
  ronald.thomas@famu.edu
• Federal Fiscal Year:
  2001
• Performing Organization:
  Deep South Center for Occupational Health and Safety, University of Alabama at Birmingham, Birmingham, AL
• Peer Reviewed:
  True
• Start Date:
  19980701
• Source Full Name:
  Oncology Reports
• End Date:
  20040630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ae657f48f653c0f9f451cad3ec957b726c16bc359803d15b5d1c49855dcee21484010f6d71d6309b999204f90a71e9a44515ed12bf54c2b997d50fb8ec0e0a02
• Download URL:
  https://stacks.cdc.gov/view/cdc/214897/cdc_214897_DS1.pdf
• File Type:
  [PDF - 1.08 MB ]