Energetics and mammary carcinogenesis: effects of moderate-intensity running and energy intake on cellular processes and molecular mechanisms in rats.
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 (physical activity, PA) or by regulating dietary energy (RE) intake relative to a sedentary control (SC) group that ate ad libitum. 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 SC, a PA group given free access to a motorized running wheel, or a RE group whose food intake limited growth to the rate observed in PA. Compared with SC, mammary carcinogenesis was inhibited by RE or PA. 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 RE and PA induced apoptosis via the mitochondrial pathway, that cell cycle progression was suppressed at the G(1)/S transition, and that intratumoral blood vessel density was reduced, although it remains to be determined whether PA and RE exert these effects via the same mechanisms.
Zhu
Zongjian
Z
Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado 80523, USA.
Jiang
Weiqin
W
McGinley
John N
JN
Thompson
Henry J
HJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D031204:Caloric Restriction; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008770:Methylnitrosourea / Q000633:toxicity; D009043:Motor Activity / Q000502:physiology*; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012420:Running
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D008770:Methylnitrosourea; D053148:Caspase 3