Abstract
2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone (ABPP) is one of the pyrimidinone compounds which induce interferon (IFN) in several animal species and have potent antivirus activities. ABPP has also been shown to exert growth inhibition of mouse B-16 melanoma and mammary carcinoma. We investigated the effectiveness of ABPP in the treatment of 7,12-dimethylbenz (α) anthracene (DMBA)-induced rat mammary cancer alone or in combination with tamoxifen. Fifty-two 50-day-old female Sprague Dawley rats were randomly divided into four groups after each rat received 25 mg of DMBA. The following treatments were started 90 days later for four weeks: Group I, 0.5 cc of 1% carboxymethyl cellulose (CMC) by intraperitoneal (ip) injection three times a week; Group II, 200 mg/kg ABPP in 0.5 cc of 1% CMC ip three times a week; Group III, 0.2 mg/kg tamoxifen in 0.5 cc peanut oil ip daily five days a week; Group IV the combination treatment of Groups II and III. Tumors were measured once every week. There were 1, 5, 6, and 12 tumors in Groups I, II, III, and IV rats, respectively, showing greater than 50% reduction in size. Numbers of new tumors developed during treatment were 10, 8, 10, and 2 (p < 0.01) in Groups I, II, III, and IV, respectively. There was no correlation between tumor response and the amount of interferon induced by ABPP. There was also no definite pattern of change in estrogen receptor content before and after ABPP treatment. Results from a logit analysis suggest that ABPP has antitumor activity against DMBAinduced rat mammary carcinoma about the same magnitude as tamoxifen. Also, the antitumor effect of the simultaneous application of ABPP and tamoxifen is additive and is probably better then either one alone.
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