Submitted on September 8, 2008
Revised on December 1, 2008
Accepted on December 15, 2008
Energetics and Mammary Carcinogenesis: Effects of Moderate Intensity Running and Restricted Energy Intake on Cellular Processes and Molecular Mechanisms in Rats
Zongjian Zhu1, Weiqin Jiang1, John N McGinley1, and Henry Thompson1*
1 Colorado State University
* To whom correspondence should be addressed. E-mail: henry.thompson{at}colostate.edu.
The objective of this experiment was to determine the effects on mammary carcinogenesis of similar limitations in energy availability either by energy expenditure due to moderate intensity running (physically active, PA) or by restricting dietary energy (RE) intake. A total of 90 female Sprague Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either a sedentary control group (SC), a PA group given free access to a motorized running wheel, or a RE group whose food intake was restricted by an amount that would limit growth to the rate observed in PA. Mammary carcinogenesis was inhibited by limitations in energy availability resulting in growth rates 92% of SC, whether they were due to increased energy expenditure or decreased energy intake. Cancer incidence, 92.6%, 77.8% and 66.7%, p=0.06, and cancer multiplicity, 3.44, 2.11, and 1.62 cancers/rat, p=0.006, in SC, RE, and PA, respectively, were reduced to a similar extent by RE and PA. Histological and western blot analyses of mammary carcinomas provided evidence that both PA and RE induced apoptosis via the mitochondrial pathway, that cell cycle progression was suppressed at the G1/S transition, and that intra-tumoral blood vessel density was reduced.
