Medicina Molecular e Genética

Effects of Obesity and 7,12-Dimethylbenz(A) Anthracene (DMBA) Treatment on Liver Cytochrome P4501A1 and 1B1 Expression in Ovariectomized Obese Zucker Rats

Abstract

Reza Hakkak, Stewart Macleod and Soheila Korourian

Obesity is a risk factor for postmenopausal breast cancer development. We have shown that obesity increases DMBA-induced mammary tumor development in intact and ovariectomized Zucker rats. Several data suggest that DMBA requires metabolic activation to exert its carcinogenic effects. The objective of this study was to investigate the effect of obesity on hepatic expression of cytochrome P450 CYP1A1 and CYP1B1 following DMBA treatment in obese and lean ovariectomized Zucker rats. Forty day-old, ovariectomized obese (n=20) and lean (n=20) Zucker rats were placed 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. All rats were sacrificed 24 hours post-DMBA treatment. Liver microsomes were prepared, and CYP1A1 and CYP1B1 expression was measured by Western blotting using goat anti-mouse CYP1A1 and CYP1B1 antibodies. DMBA treatment significantly (p<0.001) increased expression of CYP1A1 in lean and obese ovariectomized rats compared to the control group. CYP1B1 expression was not affected by obesity or DMBA. These data suggest that DMBA can increase the expression of enzymes that are responsible for DMBA metabolism in the ovariectomized Zucker rat model.