Author(s): Reza Hakkak, Saeid Shaaf, Haley Dunn, Stewart MacLeod, George Fuchs
There is a link between obesity and increased risk of breast cancer among post-menopausal women. Recently, we have shown that obesity increases the rate of the DMBA-induced mammary tumor development in intact and ovariectomized Zucker rats. Several data suggest that DMBA require metabolic activation in order to exert their carcinogenic effects. The objective of this study was to investigate the effect of obesity on hepatic expression of CYP1A1 following treatment in obese and lean ovariectomized female Zucker rats. Forty day-old, ovariectomized obese (n=20) and lean (n=20), female Zucker rats were kept on AIN-93 G diet and 10 days later were orally gavaged with either with sesame oil (control) or with 65 mg/kg DMBA in sesame oil and were sacrificed 24 hrs post-DMBA treatment. Liver microsomes were prepared and CYP 1A1 expression were measured by Western blotting using goat anti-mouse CYP 1A1. DMBA treatment significantly (p<0.001) increased expression of CYP 1A1 in lean and obese ovariectomized rats compared to control group. Obese rats had higher basal CYP 1A1 expression compared to lean rats. These data suggest that obesity can increase expression of enzymes that are responsible for DMBA metabolism using ovariectomized zucker rat model. Also, DMBA treatment will increase the expression of CYP 1A1. (Supported by Susan G. Komen Foundation and ABI to RH).