| n the early 1980's, Barbacid and colleagues established a correlation between mammary tumors, the carcinogen N-methyl-N-nitrosourea (MNU), and the activation of the cellular H-ras gene. During the same years, Beattie and colleagues discovered that mammary tumors induced by MNU at a specific part of the estrous cycle exhibited different phenotypes. Beattie hypothesized that the prevailing hormonal profile of the estrous cycle at the time of tumor initiation modulated the subsequent induction of mammary tumors.;To investigate whether or not tumor phenotype and tumor genotype can be affected by hormones of the estrous cycle, Beattie's experiments were repeated in Chapter 2. Tumors induced in proestrus and estrus did not exhibit different phenotypes in terms of incidence, latency, and tumor number per animal when compared to tumors induced in metestrus and diestrus. However, tumors induced in proestrus and estrus had a lower frequency of H-ras activation when compared to tumors induced in metestrus and diestrus. This suggested that the hormonal milieu at the time of carcinogen administration affected the genotype of the developing tumors.;Since estradiol and progesterone are the primary hormones regulating the estrous cycle, a rat mammary carcinogenesis system where the contributions of estradiol and/or progesterone can be determined was developed in Chapter 3. Ovariectomized rats which received estradiol:progesterone 140 ;Experiments in Chapter 3 support the idea that estradiol:cholesterol 30... |
