Modulation of N-nitrosomethylurea induced mammary tumorigenesis by dietary fat and voluntary exercise

The effect of dietary fat and exercise on N-nitrosomethylurea [NMU:CAS:684-93-5]-induced mammary tumorigenesis in female F344 rats was investigated. Rats were fed the NIH-07 diet until NMU administration on day 50 of age, when they were transferred to four treatment groups. Three sedentary groups were fed either high-fat (20% wt/wt), medium fat (10%) or low fat (5%) diets (HF, MF, LF, respectively), and a fourth group was fed a HF diet but allowed free access to an activity wheel (HFEX). Tumor yields among the three sedentary groups were significantly greater in the HF and MF groups when compared to the LF group. Voluntary exercise reduced tumor yields and delayed time of tumor appearance in HFEX animals to levels similar to those found in LF sedentary animals. Animals with voluntary access to exercise wheels averaged between 1.03 and 2.85 miles/day, consumed more food (+ 18%) and exhibited greater weight gain (+ 13%) than their sedentary counterparts. No differences in weight gains were detected among the HF, MF, and LF groups, despite widely varying amounts of fat intake. Body composition studies indicated that body fat content was not influenced by the quantity of fat consumed in the diet, but was significantly reduced by voluntary exercise (-20%). Since exercise and fat intake have been associated with alterations in endocrine status, circulating bioactive and immunoactive prolactin were assessed at termination. No significant changes were found in either form of prolactin among the four experimental groups, casting doubt on mediation by this pituitary hormone.