Relationship of hormones to inhibition of mammary tumor development by underfeeding during the "critical period" after carcinogen administration.

Seven days prior to 7,12-dimethylbenz(a)anthracene (DMBA) administration, virgin 50-day-old female Sprague-Dawley rats were placed on a food-restricted diet and continued on this regimen until 30 days after DMBA injection. One day prior to and 7 days after DMBA administration, animals were given daily 0.1-ml s.c. injections of 0.9% NaCl solution (controls), haloperidol (HAL; 0.5 mg/kg) to increase prolactin secretion, growth hormone (GH; 0.5 mg/kg), estradiol benzoate (EB; 1 microgram/rat), or a combination of HAL, EB, and GH. Drug and hormone treatments were terminated after 8 days, but underfeeding continued for 30 days after DMBA administration, after which time all animals were placed on ad libitum feeding for the remainder of the 26-week experiment. Food restriction for 7 days prior to and 30 days after DMBA administration resulted in a significant reduction in average tumor number and size by the end of the 26-week experiment. Treatment for 8 days with EB produced a significant increase in mammary tumor incidence despite underfeeding, whereas underfed rats given the combination of HAL EB, and GH showed development and growth of mammary tumors equal to that of full-fed controls. Both EB and HAL significantly raised blood prolactin levels. GH alone had no apparent effect on mammary tumor incidence. These results indicate that reduced food intake during the "critical period" for induction of mammary tumors in rats by DMBA can produce inhibition of mammary tumor development throughout the 6-month period of this experiment and that administration of EB or the combination of EB, HAL, and GH for only 8 days can counteract the inhibition by underfeeding.