Acceleration of Mammary Neoplasia in Aromatase Transgenic Mice by 7,12-Dimethylbenz[a]anthracene

Details

• Personal Author:
  Keshava N ; Kirma N ; Mandava U ; Tekmal RR
• Description:
  Our studies using the aromatase transgenic mice model have shown that early exposure of mammary epithelium to in situ estrogen as a result of overexpression of aromatase predispose mammary tissue to preneoplastic changes. Here, we hypothesize that the preneoplastic changes induced by mammary estrogen in aromatase transgenic females may be susceptible to environmental carcinogens like 7,12-dimethylbenz[a]anthracene (DMBA), and may result in the acceleration and/or increase in the incidence of breast cancer. Results presented in this study show that tumors appeared in 25% of the mice that were treated with DMBA and all treated transgenic animals had microscopic evidence of neoplastic progression. Control non-transgenic females did not have significant changes even after treatment with DMBA. Consistent with increased neoplastic changes in DMBA-treated aromatase mice, we have seen an increase in the expression of genes involved in cell proliferation and cell cycle. We have also seen changes in the expression of oxidative stress markers and changes in estrogen-mediated growth factors. These studies indicate that more than one event is required for tumor formation, and that early estrogen exposure leading to preneoplastic changes in the mammary epithelial cells increases susceptibility to environmental carcinogens that may result in acceleration and/or an increase in the incidence of breast cancer. [Description provided by NIOSH]
• Subjects:
  Animals Endocrine System Estrogens Neoplasms Occupational Health Safety
• Keywords:
  Animal-studies Breast-cancer Estrogenic-hormones Gene-mutation Glands Glandular-disorders Hormones Mammary-glands
• ISSN:
  0304-3835
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  125-133
• Volume:
  167
• Issue:
  2
• NIOSHTIC Number:
  nn:20032155
• Citation:
  Cancer Lett 2001 Jun; 167(2):125-133
• Contact Point Address:
  Department of Gynecology and Obstetrics, 1639 Pierce Drive, 4217 WMB, Emory University, Atlanta, GA 30322-4770, USA
• Email:
  rtekmal@emory.edu
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Cancer Letters
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/186200/cdc_186200_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]