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Fetal alcohol exposure increases mammary tumor susceptibility and alters tumor phenotype in rats.

AbstractBACKGROUND:
Altered fetal programming because of a suboptimal in utero environment has been shown to increase susceptibility to many diseases later in life. This study examined the effect of alcohol exposure in utero on N-nitroso-N-methylurea (NMU)-induced mammary cancer risk during adulthood.
METHODS:
Study 1: Pregnant Sprague Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol-fed), an isocaloric liquid diet (pair-fed), or rat chow ad libitum (ad lib-fed) from day 11 to 21 of gestation. At birth, female pups were cross-fostered to ad lib-fed control dams. Adult offspring were given an I.P. injection of NMU at a dose of 50 mg/kg body weight. Mammary glands were palpated for tumors twice a week, and rats were euthanized at 23 weeks postinjection. Study 2: To investigate the role of estradiol (E2), animals were exposed to the same in utero treatments but were not given NMU. Serum was collected during the preovulatory phase of the estrous cycle.
RESULTS:
At 16 weeks postinjection, overall tumor multiplicity was greater in the offspring from the alcohol-fed group compared to the control groups, indicating a decrease in tumor latency. At study termination, 70% of all animals possessed tumors. Alcohol-exposed animals developed more malignant tumors and more estrogen receptor-α-negative tumors relative to the control groups. In addition, IGF-binding protein-5 (IGFBP-5) mRNA and protein were decreased in tumors of alcohol-exposed animals. Study 2 showed that alcohol-fed animals had significantly increased circulating E2 when compared to either control group.
CONCLUSIONS:
These data indicate that alcohol exposure in utero increases susceptibility to mammary tumorigenesis in adulthood and suggest that alterations in the IGF and E2 systems may play a role in the underlying mechanism.
AuthorsTiffany A Polanco, Catina Crismale-Gann, Kenneth R Reuhl, Dipak K Sarkar, Wendie S Cohick
JournalAlcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 34 Issue 11 Pg. 1879-87 (Nov 2010) ISSN: 1530-0277 [Electronic] England
PMID20662802 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 by the Research Society on Alcoholism.
Chemical References
  • Central Nervous System Depressants
  • Insulin-Like Growth Factor Binding Protein 5
  • Somatomedins
  • Ethanol
  • Estradiol
  • RNA
  • Insulin-Like Growth Factor I
Topics
  • Animals
  • Blotting, Western
  • Central Nervous System Depressants (toxicity)
  • Disease Progression
  • Estradiol (physiology)
  • Ethanol (toxicity)
  • Female
  • Immunohistochemistry
  • Insulin-Like Growth Factor Binding Protein 5 (biosynthesis)
  • Insulin-Like Growth Factor I (metabolism)
  • Mammary Neoplasms, Animal (chemically induced, pathology)
  • Phenotype
  • Pregnancy
  • Prenatal Exposure Delayed Effects (pathology)
  • RNA (biosynthesis, genetics)
  • Rats
  • Rats, Sprague-Dawley
  • Somatomedins (metabolism, physiology)

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