Melatonin Inhibition and Pinealectomy Enhancement of 7,12-dimethylbenz(a)anthracene-induced Mammary Tumors in the Rat

Cancer Res. 1981 Nov;41(11 Pt 1):4432-6.

Abstract

The effects of the pineal hormone, melatonin, and of pinealectomy on the incidence of mammary adenocarcinoma in Sprague-Dawley rats treated with 7,12-dimethylbenz(alpha)-anthracene (DMBA) were investigated. Melatonin (2.5 mg/kg), begun on the same day as DMBA (5 mg) treatment and given daily in the afternoon for 90 days, significantly reduced the incidence of mammary tumors from 79% (control) to 20% (treated) (p less than 0.002). Rats pinealectomized at 20 days of age and treated with 7 mg of DMBA at 50 days of age had a higher incidence of tumors (88%) compared to control animals (22%). Fifteen mg of DMBA, which resulted in a higher incidence of tumors, reduced the difference between pinealectomized and control animals. Melatonin only partially reversed the effects of pinealectomy, reducing the incidence from 87% (pinealectomy alone) to 63% (pinealectomy plus melatonin); however, the tumor incidence was still lower (27%) in nonpinealectomized, melatonin-treated animals. Assessment of plasma prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, and cortisol in DMBA-treated tumor-free and tumor-bearing animals revealed a significantly lower plasma prolactin concentration [27 +/- 5 (S.E.) ng/ml] in melatonin-treated animals as compared to vehicle-treated animals [65 +/- 8 ng/ml]. The concentration of plasma prolactin was less in melatonin-treated, pinealectomized rats (55 +/- 10 ng/ml) as compared to vehicle-treated, pinealectomized animals (101 +/- 13 ng/ml). Other hormones were not affected by melatonin treatment. These data support the hypothesis that melatonin inhibits the development of DMBA-induced mammary tumors in the rat while removal of the pineal gland stimulates development of such tumors. Additionally, these experiments provide evidence that these effects may be mediated by a suppression of plasma prolactin levels.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene*
  • Adenocarcinoma / chemically induced
  • Adenocarcinoma / metabolism
  • Animals
  • Benz(a)Anthracenes*
  • Circadian Rhythm
  • Female
  • Mammary Neoplasms, Experimental / chemically induced*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / prevention & control
  • Melatonin / pharmacology*
  • Neoplasms, Hormone-Dependent*
  • Pineal Gland / physiology*
  • Prolactin / blood
  • Rats
  • Rats, Inbred Strains
  • Time Factors

Substances

  • Benz(a)Anthracenes
  • 9,10-Dimethyl-1,2-benzanthracene
  • Prolactin
  • Melatonin