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

Intramural Research Program, National Institute of Child Health and Human Development [L. T.], and Division of Cancer Treatment [M. C., D. R., M. L., B. C.], and Laboratory of Pathology [C. R.], National Cancer Institute, NIH, Bethesda, Maryland 20205

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()-anthracene (DMBA) were investigated. Melatonin (2.5 mg/kg), begun on the same day as DMBA (15 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 < 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.