Journal of Cancer Research and Clinical Oncology

, Volume 117, Issue 6, pp 526–532 | Cite as

Pineal melatonin inhibition of tumor promotion in theN-nitroso-N-methylurea model of mammary carcinogenesis: potential involvement of antiestrogenic mechanisms in vivo

  • David E. Blask
  • Diane B. Pelletier
  • Steven M. Hill
  • Athena Lemus-Wilson
  • David S. Grosso
  • Sean T. Wilson
  • Mark E. Wise
Original Papers Experimental Oncology


TheN-methyl-N-nitrosurea (NMU) model of hormone-responsive rat mammary carcinogenesis was used to address the hypothesis that melatonin (Mel), the principle hormone of the pineal gland, inhibits tumorigenesis by acting as an anti-promoting rather than an anti-initiating agent. Daily late-afternoon injections of Mel (500 μg/day), restricted to the initiation phase of NMU mammary tumorigenesis, were ineffective in altering tumor growth over a 20-week period. When Mel treatment was delayed for 4 weeks after NMU and then continued through the remainder of the promotion phase, only tumor number was significantly lower than in controls. However, when Mel injections encompassed the entire promotion phase, both tumor incidence and number were significantly lower than in the controls. Although elimination of the endogenous Mel signal via pinealectomy promoted tumor growth, the effect was not statistically significant. Serum levels of estradiol and tumor estrogen receptor content were unaltered by either Mel or pinealectomy. While Mel treatment failed to affect circulating prolactin levels, pinealectomy caused a two-fold increase in serum prolactin. The estradiol-stimulated recrudescence of tumors following ovariectomy was completely blocked by either 20, 100 or 500 μg Mel/day or tamoxifen (20 μg/day). Thus, Mel appears to be an antipromoting hormone that may antagonize the tumor-promoting actions of estradiol in this model of mammary tumorigenesis.

Key words

Pineal Melatonin Breast cancer Hormones N-Nitroso-N-methylurea 











estrogen receptor






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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • David E. Blask
    • 1
  • Diane B. Pelletier
    • 1
  • Steven M. Hill
    • 1
  • Athena Lemus-Wilson
    • 1
  • David S. Grosso
    • 1
  • Sean T. Wilson
    • 1
  • Mark E. Wise
    • 2
  1. 1.Departments of Anatomy, Obstetrics and GynecologyUniversity of ArizonaTucsonUSA
  2. 2.Departments of Animal Sciences and PhysiologyUniversity of ArizonaTucsonUSA
  3. 3.Medical Research InstituteThe Mary Imogene Bassett HospitalCooperstownUSA

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