Alcohol exposure in utero increases susceptibility to prostate tumorigenesis in rat offspring

Sengottuvelan Murugan, Changqing Zhang, Sepideh Mojtahedzadeh, Dipak K. Sarkar

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Prenatal alcohol exposure has been shown to increase offspring susceptibility to some chemical carcinogens. Whether prenatal exposure to alcohol makes the offspring more susceptible to the development of prostate cancer is not known. Therefore, we determined whether any functional abnormalities and increased cancer susceptibility exist in the prostate of fetal alcohol-exposed male rats during the adult period. Methods: Pregnant rats were fed with a liquid diet containing alcohol (alcohol-fed [AF]), or pair-fed with isocaloric liquid diet (PF) or ad libitum fed with rat chow (ad lib-fed). Male offspring of these rats were given N-Nitroso-N-methylurea and testosterone to induce prostate neoplasia or left untreated. Around 6 to 8 months of age, the prostates of these animals were processed for determination of biochemical changes and histopathologies. Results: Prostates of noncarcinogen treated animals that were alcohol exposed during the prenatal period demonstrated inflammatory cell infiltration and epithelial atypia and increased number of proliferative cells in the ventral lobe of this gland, but the prostate of control animal showed normal cytoarchitecture. In addition, prenatal alcohol-exposed rats showed decreased levels of cell-cell adhesion marker and increased estrogenic activity in the ventral prostate. Prenatally ethanol (EtOH)-exposed rats, when treated with carcinogen and testosterone, showed histological evidence for high-grade prostatic intraepithelial neoplasia (PIN) primarily in the ventral prostate, whereas control animals showed only low-grade PIN. Prenatally EtOH-exposed rats treated with carcinogen and testosterone also showed increased number of proliferative cells and androgen receptor with concomitant decreased levels of tumor suppressor proteins in the ventral prostate. Conclusions: These results suggest for the first time that prenatal EtOH exposures induce histophysiological changes in the prostate as well as it increases the susceptibility of the prostate to develop neoplasia during adulthood.

Original languageEnglish (US)
Pages (from-to)1901-1909
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume37
Issue number11
DOIs
StatePublished - Nov 1 2013

Fingerprint

Rats
Prostate
Carcinogenesis
Alcohols
Animals
Carcinogens
Testosterone
Nutrition
Prostatic Intraepithelial Neoplasia
Tumor Suppressor Proteins
Cell adhesion
Androgen Receptors
Liquids
Cell Count
Infiltration
Diet
Neoplasms
Ethanol
Cell Adhesion
Prostatic Neoplasms

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Keywords

  • Aromatase
  • Estrogen Receptor
  • Fetal Alcohol
  • Prostate Cancers

Cite this

Murugan, Sengottuvelan ; Zhang, Changqing ; Mojtahedzadeh, Sepideh ; Sarkar, Dipak K. / Alcohol exposure in utero increases susceptibility to prostate tumorigenesis in rat offspring. In: Alcoholism: Clinical and Experimental Research. 2013 ; Vol. 37, No. 11. pp. 1901-1909.
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Alcohol exposure in utero increases susceptibility to prostate tumorigenesis in rat offspring. / Murugan, Sengottuvelan; Zhang, Changqing; Mojtahedzadeh, Sepideh; Sarkar, Dipak K.

In: Alcoholism: Clinical and Experimental Research, Vol. 37, No. 11, 01.11.2013, p. 1901-1909.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alcohol exposure in utero increases susceptibility to prostate tumorigenesis in rat offspring

AU - Murugan, Sengottuvelan

AU - Zhang, Changqing

AU - Mojtahedzadeh, Sepideh

AU - Sarkar, Dipak K.

PY - 2013/11/1

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N2 - Background: Prenatal alcohol exposure has been shown to increase offspring susceptibility to some chemical carcinogens. Whether prenatal exposure to alcohol makes the offspring more susceptible to the development of prostate cancer is not known. Therefore, we determined whether any functional abnormalities and increased cancer susceptibility exist in the prostate of fetal alcohol-exposed male rats during the adult period. Methods: Pregnant rats were fed with a liquid diet containing alcohol (alcohol-fed [AF]), or pair-fed with isocaloric liquid diet (PF) or ad libitum fed with rat chow (ad lib-fed). Male offspring of these rats were given N-Nitroso-N-methylurea and testosterone to induce prostate neoplasia or left untreated. Around 6 to 8 months of age, the prostates of these animals were processed for determination of biochemical changes and histopathologies. Results: Prostates of noncarcinogen treated animals that were alcohol exposed during the prenatal period demonstrated inflammatory cell infiltration and epithelial atypia and increased number of proliferative cells in the ventral lobe of this gland, but the prostate of control animal showed normal cytoarchitecture. In addition, prenatal alcohol-exposed rats showed decreased levels of cell-cell adhesion marker and increased estrogenic activity in the ventral prostate. Prenatally ethanol (EtOH)-exposed rats, when treated with carcinogen and testosterone, showed histological evidence for high-grade prostatic intraepithelial neoplasia (PIN) primarily in the ventral prostate, whereas control animals showed only low-grade PIN. Prenatally EtOH-exposed rats treated with carcinogen and testosterone also showed increased number of proliferative cells and androgen receptor with concomitant decreased levels of tumor suppressor proteins in the ventral prostate. Conclusions: These results suggest for the first time that prenatal EtOH exposures induce histophysiological changes in the prostate as well as it increases the susceptibility of the prostate to develop neoplasia during adulthood.

AB - Background: Prenatal alcohol exposure has been shown to increase offspring susceptibility to some chemical carcinogens. Whether prenatal exposure to alcohol makes the offspring more susceptible to the development of prostate cancer is not known. Therefore, we determined whether any functional abnormalities and increased cancer susceptibility exist in the prostate of fetal alcohol-exposed male rats during the adult period. Methods: Pregnant rats were fed with a liquid diet containing alcohol (alcohol-fed [AF]), or pair-fed with isocaloric liquid diet (PF) or ad libitum fed with rat chow (ad lib-fed). Male offspring of these rats were given N-Nitroso-N-methylurea and testosterone to induce prostate neoplasia or left untreated. Around 6 to 8 months of age, the prostates of these animals were processed for determination of biochemical changes and histopathologies. Results: Prostates of noncarcinogen treated animals that were alcohol exposed during the prenatal period demonstrated inflammatory cell infiltration and epithelial atypia and increased number of proliferative cells in the ventral lobe of this gland, but the prostate of control animal showed normal cytoarchitecture. In addition, prenatal alcohol-exposed rats showed decreased levels of cell-cell adhesion marker and increased estrogenic activity in the ventral prostate. Prenatally ethanol (EtOH)-exposed rats, when treated with carcinogen and testosterone, showed histological evidence for high-grade prostatic intraepithelial neoplasia (PIN) primarily in the ventral prostate, whereas control animals showed only low-grade PIN. Prenatally EtOH-exposed rats treated with carcinogen and testosterone also showed increased number of proliferative cells and androgen receptor with concomitant decreased levels of tumor suppressor proteins in the ventral prostate. Conclusions: These results suggest for the first time that prenatal EtOH exposures induce histophysiological changes in the prostate as well as it increases the susceptibility of the prostate to develop neoplasia during adulthood.

KW - Aromatase

KW - Estrogen Receptor

KW - Fetal Alcohol

KW - Prostate Cancers

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