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

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.