The interaction of dietary fat and antiestrogen treatment on DMBA-induced mammary tumors in the rat.
This study was designed to determine whether an estrogenic mechanism is involved in dietary fat-modulated tumor development and growth. Female Sprague-Dawley rats were placed on a semipurified low-fat (2% fat), high-saturated fat (20% fat), or high-polyunsaturated fat (20% fat) diet at 21 days of age. A single dose of 7,12-dimethylbenz[a]anthracene (DMBA, 10 mg) was administered intragastrically at 50 days of age. Two studies were performed. One tested the effectiveness of antiestrogen treatment (either tamoxifen or analog II) on tumor development when it was given one week prior to and one week after DMBA treatment in animals consuming a high-polyunsaturated fat diet. The second six-week study tested the antiestrogen effectiveness in arresting tumor growth and in producing regressions of established DMBA-induced tumors in rats consuming various levels and types of fat. The results of these studies indicate that both antiestrogens employed reduced the rate of growth and increased the number of regressions of established DMBA-induced tumors. In general, this was true in animals fed diets with a high content of either saturated or polyunsaturated fats and to a lesser extent in animals fed a low-fat diet. Tamoxifen produced a somewhat greater reduction in the growth of established tumor than did analog II. However, analog II, which is a more biologically "pure" antiestrogen, reduced the incidence of animals with mammary tumors and total tumor burden when administered one week before and one week after DMBA dosing. Tamoxifen, which is a partial estrogen-agonist, did not alter tumor incidence, but it did reduce the total tumor burden under these same experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D004041:Dietary Fats; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; C035174:tamoxifen analog II