The primary objective of this work is to establish the time during the life cycle when dietary fat is maximally effective in altering the frequency of female reproductive system cancer. The relevance of this to human health is in relation to providing guidance on the most critical time to control dietary fat intake for cancer prevention. A second purpose of the work is to establish an animal model to investigate the mechanism of dietary fat effect on cancer, so that preventive measures can eventually be worked out for persons already programmed for an increased cancer rate due to excessive dietary fat exposure. Epidemiologic data indicate that the sensitive period to dietary fat for female reproductive system cancer is early in life. Preliminary results with an experiment on mice indicates that the period from shortly before to shortly after pregnancy covers a developmental stage of exceptional sensitivity to the programming of cancer by dietary fat. A more exact demonstration of the sensitive period will be attempted by : (1) embryo transfers tp test for a germ cell effect. (2) high fat exposure limited to fetal development to test this period specifically, and (3) a fostering experiment to test the nursing period. In all cases, animals exposed to low fat diet will be compared to animals exposed to a high fat diet. In addition, the possibility of a multigenerational and cumulative effect will be explored by raising second generation offspring without, or with exposure to high and low fat diets during the second pregnancy. An inherent advantage to these experiments is the establishment of an animal model for studies on the mechanisms by which early exposure to a high fat diet programs the individual for an increased susceptibility to cancer later in life. The test subjects utilized in the experiment that produced the preliminary results were female offspring of female CD-1 mice exposed prenatally to diethylstilbestrol. These second generation offspring have an increased susceptibility to uterine cancer and high dietary fat produces an increased cancer rate of sufficient magnitude to keep the required number of test subjects within practical limits.
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