Faculty Collaboration Database

Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats. Breast Cancer Res 2005;7(5):R627-33

Date

09/20/2005

Pubmed ID

16168107

Pubmed Central ID

PMC1242129

DOI

10.1186/bcr1263

Scopus ID

2-s2.0-33644877245 (requires institutional sign-in at Scopus site)   66 Citations

Abstract

INTRODUCTION: High body mass index has been associated with increased risk for various cancers, including breast cancer. Here we describe studies using 7,12-dimethylbenz(a)anthracene (DMBA) to investigate the role of obesity in DMBA-induced mammary tumor susceptibility in the female Zucker rat (fa/fa), which is the most widely used rat model of genetic obesity.

METHOD: Fifty-day-old female obese (n = 25) and lean (n = 28) Zucker rats were orally gavaged with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors. Rats were killed 139 days after DMBA treatment.

RESULTS: The first mammary tumor was detected in the obese group at 49 days after DMBA treatment, as compared with 86 days in the lean group (P < 0.001). The median tumor-free time was significantly lower in the obese group (P < 0.001). Using the days after DMBA treatment at which 25% of the rats had developed mammary tumors as the marker of tumor latency, the obese group had a significantly shorter latency period (66 days) than did the lean group (118 days). At the end of the study, obese rats had developed a significantly (P < 0.001) greater mammary tumor incidence (68% versus 32%) compared with the lean group. The tumor histology of the mammary tumors revealed that obesity was associated with a significant (P < 0.05) increase in the number of rats with at least one invasive ductal and lobular carcinoma compared with lean rats.

CONCLUSION: Our results indicate that obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis.

Author List

Hakkak R, Holley AW, Macleod SL, Simpson PM, Fuchs GJ, Jo CH, Kieber-Emmons T, Korourian S

Author

Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

9,10-Dimethyl-1,2-benzanthracene
Animals
Female
Mammary Neoplasms, Experimental
Obesity
Overweight
Rats
Rats, Sprague-Dawley
Rats, Zucker
Thinness