Histological analysis of low dose NMU effects in the rat mammary gland.
BACKGROUND
Our objective was to assess the histological changes in mammary glands of the female Wistar-Furth rat as a result of low dose exposure to N-nitrosomethylurea (NMU).


METHODS
Groups of 30-40 virgin female rats of between 49-58 days old received a single injection of 10, 20, 30 or 50 mg NMU/kg body weight (BW). A group of 10 control rats received 0.9% NaCl solution only. The formation of palpable mammary gland tumors was assessed weekly and, upon sacrifice at 12, 22 and 25-30 weeks after treatment, we performed a comprehensive histological analysis of all mammary gland lesions and tumors.


RESULTS
Alongside the predicted increase in tumor number and decrease in tumor latency with increasing NMU dose, we observed a number of microscopic lesions and other epithelial abnormalities in the mammary glands for all NMU doses. Two types of non-neoplastic histological changes were observed in rats exposed to 10 or 20 mg NMU/kg BW: namely, (i) an increase in the number of acinar structures often accompanied by secretion into the lumen which is normally associated with pregnancy and lactation, and (ii) an increase in the number of epithelial cells sloughed into the lumen of the epithelial ducts.


CONCLUSIONS
This study establishes a baseline for low-dose exposure and defines the histological features in the mammary gland resulting from NMU exposure. Furthermore, this system provides an ideal platform for evaluating the relative susceptibility of animals protected from, or predisposed to, developing cancer through environmental influences.
Murray
Tessa J
TJ
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, USA. tessa.murray@tufts.edu
Ucci
Angelo A
AA
Maffini
Maricel V
MV
Sonnenschein
Carlos
C
Soto
Ana M
AM
D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects*; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D008770:Methylnitrosourea / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013997:Time Factors
D008770:Methylnitrosourea