Wheel running, skeletal muscle aerobic capacity and 1-methyl-1-nitrosourea induced mammary carcinogenesis in the rat.

Emerging evidence indicates that intrinsic differences and induced changes in aerobic capacity are probably to play a critical role in the development of chronic diseases like cancer. This study was initiated: (i) to determine how citrate synthase activity, which is routinely used as a marker of aerobic capacity and mitochondrial density in skeletal muscle, was affected by voluntary running on either a motorized activity wheel or a non-motorized free wheel and (ii) to investigate the association between aerobic capacity and the carcinogenic response induced in the mammary gland by intraperitoneal injection of 1-methyl-1-nitrosurea. Overall, wheel running reduced cancer incidence (96 versus 72%, P = 0.0006) and the number of cancers per animal (2.84 versus 1.78, P < 0.0001) and induced citrate synthase activity (276 versus 353 U/mg, P < 0.0001, sedentary control versus wheel running,respectively). Both motorized and free wheel running increased citrate synthase activity (373 +/- 24, 329 +/- 11 and 276 +/- 9 U/mg protein, P < 0.0001) and reduced the average number of cancers per rat (2.84, 1.96 and 1.63, P < 0.01), sedentary control, free wheel and motorized wheel, respectively. However, regression analyses failed to provide evidence of a significant association between citrate synthase activity and either cancer incidence or cancer multiplicity. Citrate synthase activity is a single measure in a complex pathway that determines aerobic capacity. The multifaceted nature of intrinsic and inducible aerobic capacity limits the usefulness of citrate synthase activity alone in elucidating the relationship between aerobic capacity and the carcinogenic response.