Chemoprevention of MNU-induced mammary tumors in the mature rat by 4-HPR and tamoxifen

Anticancer Res. 1992 Jul-Aug;12(4):1147-53.


The chemopreventive efficacies of the retinoid all-trans-N-(4-hydroxyphenyl)-retinamide (4-HPR) and the anti-estrogen tamoxifen citrate were evaluated against N-methyl-N'-nitrosourea (MNU) induced mammary cancer in 120-day old female Sprague-Dawley rats. The agents were tested alone and in combination. They were administered in a modified AIN-76A diet, beginning 60 days prior to a single i.v. dose of 50 mg MNU/kg-bw and continuing until the end of the study, 180 days post-carcinogen treatment. At 782 mg/kg diet, 4-HPR alone significantly inhibited the induction of mammary adenocarcinomas compared with carcinogen controls. At 0.250 mg/kg diet, tamoxifen alone reduced tumor incidence compared with carcinogen controls. At 0.125 mg/kg diet, tamoxifen was ineffective. Combinations of 782 mg 4-HPR/kg diet with either 0.250 or 0.125 mg tamoxifen/kg diet were effective in inhibiting MNU-induced adenocarcinomas. The reductions in tumor incidence were greater for these combinations than for either agent alone. 4-HPR and 0.250 mg tamoxifen/kg diet decreased tumor incidence 81% (p less than 0.005), whereas 4-HPR and 0.125 mg tamoxifen/kg diet decreased tumor incidence 72% (p less than 0.005) compared with carcinogen controls. The combination of 391 mg 4-HPR/kg diet and 0.500 mg tamoxifen/kg diet was also tested and was effective in reducing tumor incidence.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Screening Assays, Antitumor
  • Female
  • Fenretinide
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / prevention & control*
  • Methylnitrosourea
  • Rats
  • Rats, Inbred Strains
  • Tamoxifen / administration & dosage
  • Tretinoin / administration & dosage
  • Tretinoin / analogs & derivatives


  • Tamoxifen
  • Fenretinide
  • Tretinoin
  • Methylnitrosourea