Alcohol Exposure in Utero Increases Susceptibility to Prostate Tumorigenesis in Rat Offspring
Article first published online: 26 JUL 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 11, pages 1901–1909, November 2013
How to Cite
Murugan, S., Zhang, C., Mojtahedzadeh, S. and Sarkar, D. K. (2013), Alcohol Exposure in Utero Increases Susceptibility to Prostate Tumorigenesis in Rat Offspring. Alcoholism: Clinical and Experimental Research, 37: 1901–1909. doi: 10.1111/acer.12171
- Issue published online: 24 OCT 2013
- Article first published online: 26 JUL 2013
- Manuscript Accepted: 15 MAR 2013
- Manuscript Received: 9 OCT 2012
- National Institute of Health. Grant Number: R37AA08757
- Estrogen Receptor;
- Fetal Alcohol;
- Prostate Cancers
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.
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.
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.
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.