Treatment of 7,12-dimethylbenz (α) anthracene (DMBA)-induced rat mammary cancer by 2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone (ABPP) ± tamoxifen

Alex Y Chang, K. J. Pandya, D. A. Stringfellow, C. Chuang

Research output: Contribution to journalArticle

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 late 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 DMBA-induced 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 than either one alone.

Original languageEnglish (US)
Pages (from-to)299-304
Number of pages6
JournalJournal of Interferon Research
Volume3
Issue number3
StatePublished - 1983
Externally publishedYes

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Tamoxifen
Breast Neoplasms
Carboxymethylcellulose Sodium
Interferons
Neoplasms
Pyrimidinones
Therapeutics
Intraperitoneal Injections
Estrogen Receptors
Sprague Dawley Rats
Melanoma
anthracene
4(3H)-pyrimidinone
Growth

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Treatment of 7,12-dimethylbenz (α) anthracene (DMBA)-induced rat mammary cancer by 2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone (ABPP) ± tamoxifen. / Chang, Alex Y; Pandya, K. J.; Stringfellow, D. A.; Chuang, C.

In: Journal of Interferon Research, Vol. 3, No. 3, 1983, p. 299-304.

Research output: Contribution to journalArticle

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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 late 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 DMBA-induced 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 than either one alone.",
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