title: Prevention of tumorigenesis in mice by exercise is dependent on strain background and timing relative to carcinogen exposure.
abstract: Among cancer diagnoses, colorectal cancer (CRC) is prevalent, with a lifetime risk of developing CRC being approximately 5%. Population variation surrounding the mean risk of developing CRCs has been associated with both inter-individual differences in genomic architecture and environmental exposures. Decreased risk of CRC has been associated with physical activity, but protective responses are variable. Here, we utilized a series of experiments to examine the effects of genetic background (strain), voluntary exercise (wheel running), and their interaction on azoxymethane (AOM)-induced intestinal tumor number and size in mice. Additionally, we investigated how the timing of exercise relative to AOM exposure, and amount of exercise, affected tumor number and size. Our results indicated that voluntary exercise significantly reduced tumor number in a strain dependent manner. Additionally, among strains where exercise reduced tumor number (A/J, CC0001/Unc) the timing of voluntary exercise relative to AOM exposure was crucial. Voluntary exercise prior to or during AOM treatment resulted in a significant reduction in tumor number, but exercise following AOM exposure had no effect. The results indicate that voluntary exercise should be used as a preventative measure to reduce risk for environmentally induced CRC with the realization that the extent of protection may depend on genetic background.
authors.affiliation: Department of Zoology, Ohio Wesleyan University, Delaware, Ohio 43015, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Kelly
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Liyang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Jung
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Kunjie
authors.initials: K
authors.lastname: Hua
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, USA.|Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Threadgill
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Yunjung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Fernando Pardo Manuel
authors.initials: FP
authors.lastname: de Villena
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pomp
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000378:metabolism*; D063646:Carcinogenesis / Q000139:chemically induced*; D002273:Carcinogens / Q000378:metabolism*; D000068617:Genetic Background; D007414:Intestinal Neoplasms / Q000517:prevention & control*; D051379:Mice; D010805:Physical Conditioning, Animal / Q000379:methods*
chemical_list: D002273:Carcinogens; D001397:Azoxymethane