Cancer Prevention Laboratory, Colorado State University, 1173 Campus Delivery, Fort Collins, CO 80523, USA.
Carcinogenesis. 2010 Jul;31(7):1279-83. doi: 10.1093/carcin/bgq063. Epub 2010 Mar 18.
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.
新出现的证据表明，有氧能力的内在差异和诱导变化可能在癌症等慢性疾病的发展中起关键作用。本研究旨在：(i)确定柠檬酸合酶活性（通常用作骨骼肌有氧能力和线粒体密度的标志物）如何受到电动活动轮或非电动自由轮自愿跑步的影响；(ii)研究有氧能力与腹腔注射 1-甲基-1-亚硝脲诱导的乳腺致癌反应之间的关联。总的来说，轮式跑步降低了癌症发病率（96%对 72%，P=0.0006）和每只动物的癌症数量（2.84 对 1.78，P<0.0001），并诱导柠檬酸合酶活性（276 对 353 U/mg，P<0.0001，分别为静止对照组和轮式跑步组）。电动轮和自由轮跑步均增加了柠檬酸合酶活性（373±24、329±11 和 276±9 U/mg 蛋白，P<0.0001），并降低了每只大鼠的平均癌症数量（2.84、1.96 和 1.63，P<0.01），分别为静止对照组、自由轮和电动轮。然而，回归分析未能提供柠檬酸合酶活性与癌症发病率或癌症多发性之间存在显著关联的证据。柠檬酸合酶活性是决定有氧能力的复杂途径中的单一测量值。内在和可诱导有氧能力的多面性限制了柠檬酸合酶活性在阐明有氧能力与致癌反应之间关系方面的单独使用。
