Effects of high dietary fat on the growth and development of ovarian-independent carcinogen-induced mammary tumors in rats.
This study examined the influence of high dietary fat intake on the development of ovarian-independent mammary tumors in both vehicle-treated controls and rats made deficient in estrogen and prolactin during tumor induction. The majority of 7,12-dimethylbenz(a) anthracene (DMBA)-induced mammary tumors in rats are dependent on estrogen and prolactin for growth, and suppression of prolactin and estrogen at the time of tumor initiation causes a reduction in tumor incidence and increase in tumor latency. However, the majority of mammary tumors which do develop in these animals exhibit ovarian-independent growth. Sprague-Dawley rats were given 7.5 mg DMBA p.o. at 57 days of age. Starting 1 day prior to and continuing for 7 days after DMBA administration, rats were given daily injection of vehicle or the combination of tamoxifen (20 micrograms/rat) plus bromocryptine (5 mg/kg). At the end of drug treatment, rats in each treatment group were equally divided and placed on normal fat (5% corn oil) or high fat (20% corn oil) diets for the duration of the experiment. Vehicle-treated rats were ovariectomized 27 wk and drug-treated rats 47 wk after DMBA administration to determine tumor ovarian dependency. Vehicle-treated rats fed high fat diets showed significant increases in mammary tumor incidence and number as compared to similarly treated rats fed a normal fat diet, with approximately 80% of the tumors in each group being ovarian dependent. Likewise, tamoxifen-bromocryptine-treated rats fed a high fat diet showed a significant enhancement in mammary tumor number, although not incidence, as compared to similarly treated rats fed a normal diet. Tumors in these drug-treated groups displayed essentially the same incidence of ovarian dependence (23%). Tamoxifen-bromocryptine-treated groups displayed a 2-fold increase in latency of tumor appearance as compared to vehicle-treated controls; however, this long latency was not reduced when these rats were fed a high fat diet. These results demonstrate that high dietary fat stimulates ovarian-dependent and -independent mammary tumorigenesis in rats but does not influence the hormonal responsiveness of these tumors.
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D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D004041:Dietary Fats / Q000009:adverse effects*; D004967:Estrogens / Q000502:physiology; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology; D011388:Prolactin / Q000502:physiology; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology
D004041:Dietary Fats; D004967:Estrogens; D013629:Tamoxifen; D001971:Bromocriptine; D015127:9,10-Dimethyl-1,2-benzanthracene; D011388:Prolactin