Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats

Reza Hakkak, Andy W. Holley, Stewart L. MacLeod, Pippa M. Simpson, George J. Fuchs, Chan Hee Jo, Thomas Kieber-Emmons, Soheila Korourian

Research output: Contribution to journalArticlepeer-review

63 Scopus 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.

Original languageEnglish
Article numberR627
JournalBreast Cancer Research
Volume7
Issue number5
DOIs
StatePublished - Jun 6 2005

Bibliographical note

Publisher Copyright:
© 2005 Hakkak et al.; licensee BioMed Central Ltd.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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