Access to Exercise

Abstract

The incidence of spontaneous tumors in Sprague-Dawley rats has ranged from 45–71% with female rats having double the percentage compared with males. Mammary tumors account for most of the tumors. Tumors may induce cancer and other life-shortening diseases, making the study of tumor development and prevention a thriving area of research. It is unknown how the gene-environment interaction influences spontaneous tumor development. Animals that reside solely in a standard cage are extremely sedentary and this trait may enhance tumerigenesis. On the other hand, animals with access to physical activity may inhibit tumor development. PURPOSE: This study compared tumorigenesis-related gene expression and the number, size, and age-associated incidence of spontaneous mammary tumors in female Sprague-Dawley rats with different access to physical activity: 1) none outside a standard cage, (SED) 2) twice-weekly physical activity in a large box (PA), and 3) regular running wheel exercise (EX). METHODS: 108 female rats were divided into three treatment groups and investigated and compared for tumor growth and development. Affymetrix microarray and RMA expression analysis identified genes with significant >2 fold changes in gene expression. Real-time quantitative reverse transcriptase polymerase chain reaction (qPCR) was used for microarray verification. RESULTS: Palpable tumors began to develop in all groups at around 59 weeks. SED animals had tumors that were greater in number and size compared with PA and EX. At 98 weeks, 14 EX rats had 36 tumors, 22 PA rats had 52 tumors, and 23 SED rats had 66 tumors. At 98 weeks, the SED group had the lowest percentage of tumor free survival compared with PA and EX. Transforming growth factor alpha (TGF?) and Rab40c (a member of the RAS oncogene family) were 2 fold greater in expression in EX than in SED (p <0.05). CONCLUSION: Animals that resided solely in cages with no access to physical activity outside a cage, demonstrated greater number and size of spontaneous mammary tumors while access to physical activity and exercise for almost two years reduced spontaneous tumorigenesis in female rats. Surprisingly, TGFα and Rab40c, both of which are associated with tumorigenesis and carcinogenesis, were up-regulated in the exercised animals.