title: Alcohol exposure in utero increases susceptibility to prostate tumorigenesis in rat offspring.
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.
authors.affiliation: Endocrine Program, Department of Animal Sciences , Rutgers, The State University of New Jersey, New Brunswick, New Jersey.
authors.forename: Sengottuvelan
authors.initials: S
authors.lastname: Murugan
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhang
authors.forename: Sepideh
authors.initials: S
authors.lastname: Mojtahedzadeh
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Sarkar
mesh_terms: D020751:Alcohol-Induced Disorders / Q000209:etiology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D063646:Carcinogenesis / Q000139:chemically induced; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002492:Central Nervous System Depressants; D047628:Estrogen Receptor alpha; D000431:Ethanol; D001141:Aromatase
keywords: Aromatase; Estrogen Receptor; Fetal Alcohol; Prostate Cancers
references.citation: Cancer Cell. 2006 May;9(5):367-78
references.pmid: 16697957
references.citation: Biol Pharm Bull. 2006 Feb;29(2):375-9
references.pmid: 16462049
references.citation: Front Biosci. 2006 May 01;11:1388-413
references.pmid: 16368524
references.citation: Brain Res. 1992 Nov 6;595(1):17-24
references.pmid: 1467954
references.citation: JAMA. 2001 Nov 7;286(17):2143-51
references.pmid: 11694156
references.citation: Br J Cancer. 2004 Jun 1;90(11):2225-31
references.pmid: 15150620
references.citation: Carcinogenesis. 2002 Oct;23(10):1701-11
references.pmid: 12376480
references.citation: Alcohol. 1992 Nov-Dec;9(6):465-71
references.pmid: 1472301
references.citation: Cancer Lett. 2009 Sep 18;282(2):125-36
references.pmid: 19185987
references.citation: Cancer Epidemiol Biomarkers Prev. 2000 Feb;9(2):221-3
references.pmid: 10698486
references.citation: Hum Mutat. 2003 Sep;22(3):183-98
references.pmid: 12938083
references.citation: Cancer. 2004 Nov 15;101(10 Suppl):2371-490
references.pmid: 15495199
references.citation: Differentiation. 2011 Nov-Dec;82(4-5):184-99
references.pmid: 21620560
references.citation: Urology. 2001 Apr;57(4 Suppl 1):31-8
references.pmid: 11295592
references.citation: Horm Cancer. 2011 Aug;2(4):239-48
references.pmid: 21761112
references.citation: Eur Urol. 1999;35(5-6):464-7
references.pmid: 10325506
references.citation: Prostate. 1992;20(4):339-53
references.pmid: 1535126
references.citation: Differentiation. 2008 Jul;76(6):641-59
references.pmid: 18462433
references.citation: J Appl Toxicol. 2007 Jul-Aug;27(4):391-8
references.pmid: 17299812
references.citation: Cancer Causes Control. 1992 Sep;3(5):419-25
references.pmid: 1525322
references.citation: Prev Med. 1980 Mar;9(2):174-9
references.pmid: 7383982
references.citation: Hum Exp Toxicol. 2009 Apr;28(4):203-8
references.pmid: 19734271
references.citation: Semin Urol Oncol. 1996 Aug;14(3):149-55
references.pmid: 8865477
references.citation: Br J Cancer. 1994 Feb;69(2):327-32
references.pmid: 8297729
references.citation: Cancer Res. 2011 Oct 1;71(19):6282-91
references.pmid: 21835894
references.citation: Eur Urol. 2009 Mar;55(3):533-42
references.pmid: 19013008
references.citation: Alcohol Clin Exp Res. 2010 Nov;34(11):1879-87
references.pmid: 20662802
references.citation: Urology. 2004 Oct;64(4):717-22
references.pmid: 15491708
references.citation: Prostate. 2009 Feb 1;69(2):133-41
references.pmid: 18819100
references.citation: Cancer Res. 1992 May 15;52(10):2916-22
references.pmid: 1581909
references.citation: Cancer. 2009 Aug 15;115(16):3661-9
references.pmid: 19598210
references.citation: Hum Pathol. 1992 Mar;23(3):273-9
references.pmid: 1555838
references.citation: Obstet Gynecol. 1980 Nov;56(5):537-42
references.pmid: 7432722
references.citation: Ital J Anat Embryol. 1998;103(4 Suppl 1):237-52
references.pmid: 11315954
references.citation: Prostate. 2008 May 15;68(7):728-39
references.pmid: 18302197
references.citation: Cancer Causes Control. 2003 May;14(4):347-55
references.pmid: 12846366
references.citation: Reprod Fertil Dev. 2001;13(4):285-96
references.pmid: 11800167
references.citation: J Natl Cancer Inst. 1988 Sep 7;80(13):1045-53
references.pmid: 2457709
references.citation: Nutr Cancer. 2006;56(1):50-6
references.pmid: 17176217
references.citation: J Steroid Biochem Mol Biol. 2010 Feb 28;118(4-5):246-51
references.pmid: 19896534
references.citation: Br J Cancer. 2001 Nov 30;85(11):1700-5
references.pmid: 11742491
references.citation: Hum Pathol. 1992 Mar;23(3):242-8
references.pmid: 1372878