International Journal of Biological Sciences

Impact factor
3.873

ISSN 1449-2288

News feeds of IJBS published articles
My Manuscript
My Account

Journal of Biomedicinenew

Theranostics

International Journal of Medical Sciences

Journal of Cancer

Oncomedicine

Journal of Genomics

Journal of Bone and Joint Infection (JBJI)

Nanotheranostics

PubMed Central Indexed in Journal Impact Factor

Int J Biol Sci 2007; 3(7):408-416. doi:10.7150/ijbs.3.408

Research Paper

Charles River Sprague Dawley Rats Lack Early Age-Dependent Susceptibility to DMBA-Induced Mammary Carcinogenesis

R.B. Gear 1, M. Yan 1, J. Schneider 1, P. Succop 3, S.C. Heffelfinger 2, D.J. Clegg 1

1. Department of Psychiatry, University of Cincinnati, PO Box 670559, Cincinnati, OH 45267-0559, USA
2. Department of Pathology, University of Cincinnati, Cincinnati, Ohio, USA
3. Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267-0056, USA

Abstract

Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The “window of susceptibility” to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), in a single oral dose yields maximal mammary tumor formation when administered in this “window”. We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CDR IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50) developed carcinoma in situ (CIS) within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CDR IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.

Keywords: DMBA, mammary carcinogenesis, Charles River Sprague Dawley rats

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Gear RB, Yan M, Schneider J, Succop P, Heffelfinger SC, Clegg DJ. Charles River Sprague Dawley Rats Lack Early Age-Dependent Susceptibility to DMBA-Induced Mammary Carcinogenesis. Int J Biol Sci 2007; 3(7):408-416. doi:10.7150/ijbs.3.408. Available from http://www.ijbs.com/v03p0408.htm