Prevention of methylnitrosourea-induced mammary cancers by 9-cis-retinoic acid and/or vitamin D3

  • Authors:
    • Mark B. Cope
    • Vernon E. Steele
    • Isao Eto
    • Margaret M. Juliana
    • Donald L. Hill
    • Clinton J. Grubbs
  • View Affiliations

  • Published online on: May 1, 2002     https://doi.org/10.3892/or.9.3.533
  • Pages: 533-537
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Abstract

Two cancer chemopreventive agents, vitamin D3 and 9-cis-retinoic acid (9-cis-RA), were evaluated alone and in combination in the methylnitrosourea (MNU)-induced mammary cancer model. In this study, female Sprague-Dawley rats received MNU (50 mg/kg BW) at 50 days of age. Vitamin D3 and 9-cis-RA were administered in the diet beginning three days later. The groups were: Group 1, vehicle only; Group 2, 9-cis-RA (60 mg/kg diet); Group 3, vitamin D3 (10 μg/kg diet); Group 4, vitamin D3 (3.3 μg/kg diet); Group 5, 9-cis-RA (60 mg/kg diet) plus vitamin D3 (10 μg/kg diet); and Group 6, 9-cis-RA (60 mg/kg diet) plus vitamin D3 (3.3 μg/kg diet). Animals were observed daily for signs of toxicity and were palpated 2x/week for mammary tumors. The study was terminated 150 days after treatment with MNU. The average number of mammary cancers was 6.7 in the animals receiving only the carcinogen. 9-cis-RA alone caused a 23% decrease in mammary cancer multiplicity, while vitamin D3 alone actually caused slight increases of 17 and 16% at 10 and 3.3 μg/kg diet dose levels, respectively. When the agents were given in combination, however, the 9-cis-RA plus the high dose of vitamin D caused a statistically significant decrease (44%) in mammary cancer number, while the 9-cis-RA plus the low dose resulted in a 37% decrease. Thus, low doses of these agents that were not effective in preventing mammary cancer when given alone appeared to be active when given in combinations. Possible interactions between the retinoic acid receptors and vitamin D receptor may be responsible for the observed inhibition of mammary carcinogenesis.

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May-June 2002
Volume 9 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Cope MB, Steele VE, Eto I, Juliana MM, Hill DL and Grubbs CJ: Prevention of methylnitrosourea-induced mammary cancers by 9-cis-retinoic acid and/or vitamin D3. Oncol Rep 9: 533-537, 2002
APA
Cope, M.B., Steele, V.E., Eto, I., Juliana, M.M., Hill, D.L., & Grubbs, C.J. (2002). Prevention of methylnitrosourea-induced mammary cancers by 9-cis-retinoic acid and/or vitamin D3. Oncology Reports, 9, 533-537. https://doi.org/10.3892/or.9.3.533
MLA
Cope, M. B., Steele, V. E., Eto, I., Juliana, M. M., Hill, D. L., Grubbs, C. J."Prevention of methylnitrosourea-induced mammary cancers by 9-cis-retinoic acid and/or vitamin D3". Oncology Reports 9.3 (2002): 533-537.
Chicago
Cope, M. B., Steele, V. E., Eto, I., Juliana, M. M., Hill, D. L., Grubbs, C. J."Prevention of methylnitrosourea-induced mammary cancers by 9-cis-retinoic acid and/or vitamin D3". Oncology Reports 9, no. 3 (2002): 533-537. https://doi.org/10.3892/or.9.3.533