Investigating the effects of exercise on initiation of nitrosomethylurea induced mammary tumorigenesis in young rats
Year: 1996
Type: dissertation
Abstract: It has been suggested by epidemiological studies that exercise during the college years decreases the risk of breast cancer. The susceptibility of the mammary gland to carcinogenic attack depends on many factors including: 1) developmental stage of the mammary gland; 2) proliferation rate of epithelial cells; and 3) DNA damage. The purpose of t h s thesis was to assess the effects of exercise in young female Sprague Dawley rats on mammary gland development, carcinogen distribution, binding and darnage,and subsequent tumor development. Rats were run on motorized treadmills for four weeks (from twenty one to fifty days of age). Exercise had no effect on mammary gland development, although exercise significantly increased the proliferation rate of the mammary gland epithelial cells. The increased proliferation rate did not affect the amount of Nitrosomethylurea (NMU)induced DNA damage as indicated by the nick translation assay. Increasing the amount of NMU injected ( 25, 37.5 or 50 mgkg) resulted in a dose response in terms of NMU in both the liver and serum. This relationship was apparent at the mammary gland DNA level. However, DNA damage did not increase with increasing doses of NMU. When individual glands were examined, abdominal mammary glands had a lower incorporation of NMU than thoracic or inguinal glands for any concentration of NMU. Of particular interest was the finding that DNA damage was also signficantly lower in the abdominal mammary glands. We tested the effects of exercise prior to carcinogen administration on subsequent tumor development at two doses of NMU. At the higher dose (50 mg/kg) exercise significantly lowered the tumor multiplicity. However at the lower dose (37.5 mglkg) this effect was not seen. At either dose there was no effect on incidence or latency. At a dose of 37.5 mgkg, exercise significantly increased the growth rate and final tumor weights. Due to these differences in growth rates and final tumor weights we assessed the amount of insulin-like growth factor I receptor and estrogen receptor proteins in exercised and sedentary tumors as well as in normal mammary gland tissue. There was a significant increase in the content of both receptors in the tumors relative to the normal tissue. There was a significant difference in receptor content between tumors derived from exercised and sedentary rats when expressed per milligram tissue. This difference was lost when the receptor content was expressed per microgram protein. This thesis suggests that exercise prior to carcinogen administration does effect tumor outcome in a somewhat dose dependent manner. Although exercise increases the proliferation rate of mammary epithelial cells there is no effect on DNA damage or final tumor outcome. This suggests that other mechanisms must compensate for the increased proliferation.
Source: Summit (Simon Fraser University)
Author: Karen S. Whittal
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2230362540