Journal of Neural Transmission

, Volume 67, Issue 1–2, pp 125–138 | Cite as

Inhibitory effects of the pineal hormone melatonin and underfeeding during the promotional phase of 7,12-dimethylbenzanthracene-(DMBA)-induced mammary tumorigenesis

  • D. E. Blask
  • S. M. Hill
  • K. M. Orstead
  • J. S. Massa
Original Papers

Summary

The effects of melatonin (Mel) and/or underfeeding (30% food restriction) on 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumorigenesis were examined in female Sprague-Dawley rats fed a semipurified diet. During the promotional phase of tumorigenesis, the animals began receiving either daily afternoon Mel (250μg) or saline vehicle injections s.c. for 15 weeks. As compared with fed animals, underfed rats had a lower tumor incidence, tumor number and size while the latency to onset and regression of tumors was increased. Melatonin in fed rats moderately suppressed tumor incidence and number. However, the combination of Mel treatment and underfeeding caused the most marked inhibition of tumorigenesis as compared with either treatment alone. These results indicate that Mel administration and/or underfeeding during the promotional phase inhibit DMBA-induced mammary tumorigenesis perhaps via neuroendocrine and/or peripheral endocrine mechanisms.

Key words

Pineal gland melatonin underfeeding mammary cancer 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aubert C, Janiaud P, Lecalvez J (1980) Effect of pinealectomy and melatonin on mammary tumor growth in Sprague-Dawley rats under different conditions of lighting. J Neural Transm 47: 121–130Google Scholar
  2. Blask DE (1981) Potential sites of action of pineal hormones within the neuroendocrine-reproductive axis. In: Reiter RJ (ed) The pineal gland, vol II, reproduction. CRC Press, Boca Raton, pp 189–216Google Scholar
  3. Blask DE (1984) The pineal: an oncostatic gland? In: Reiter RJ (ed) The pineal gland. Raven Press, New York, pp 253–284Google Scholar
  4. Blask DE, Hill SM (1986) Effects of melatonin on cancer: studies on MCF-7 human breast cancer cells in culture. In: Wurtman RJ, Waldhauser F (eds) Melatonin in humans. Proceedings of the first international conference on melatonin in humans, Vienna, Austria, November 7–9, 1985. Springer, Wien New York, pp 433–449 (J Neural Transm [suppl] 21)Google Scholar
  5. Blask DE, Nodelman JL, Leadem CA, Richardson BA (1980) Influence of exogenously administered melatonin on the reproductive system and prolactin levels in underfed male rats. Biol Reprod 22: 507–512Google Scholar
  6. Blask DE, Leadem CA, Richardson BA (1981) Nutritional status, time of day and pinealectomy: factors influencing the sensitivity of the neuroendocrine-reproduction axis of the rat to melatonin. Horm Res 14: 104–113Google Scholar
  7. Byrkit DR (1980) Elements of statistics: an introduction to probability and statistical inference, 3rd edn. Van Nostrand, New YorkGoogle Scholar
  8. Herbert DC, Reiter RJ (1981) Influence of protein-calorie malnutrition on the circadian rhythm of pineal melatonin in the rat. Proc Soc Exp Biol Med 166: 360–363Google Scholar
  9. Hill SM, Blask DE (1985) Physiological concentrations of melatonin inhibit the proliferation of MCF-7 human breast cancer cellsin vitro. Prog 67th ann mtg endocr soc abst 1010, p 253Google Scholar
  10. Kothari LS, Shah PN, Mhatre MC (1984) Pineal ablation in varying photoperiods and the incidence of 9,10-dimethyl-1,2-benzanthracene-induced mammary cancer in rats. Cancer Letts 22: 99–102Google Scholar
  11. Lapin V (1978) Effects of reserpine on the incidence of 9,10-dimethyl-1,2- benzanthracene-induced tumors in pinealectomized and thymectomized rats. Oncology 35: 132–135Google Scholar
  12. Lima FB, Hell NS, Timo-Iaria C, Scivoletto R, Dolnikoff MS, Pupo AA (1981) Metabolic consequences of food restriction in rats. Physiol Behav 27: 115–123Google Scholar
  13. Lipsett MB (1982) Carcinogenesis of endocrine-related human cancers: interactions of diet and nutrition with the endocrine system. In: Arnott MS, van Eys J, Wang Y-M (eds) Molecular interrelations of nutrition and cancer. Raven Press, New York, pp 61–69Google Scholar
  14. Meites J (1980) Relation of the neuroendocrine system to the development and growth of experimental mammary tumors. J Neural Transm 48: 25–42Google Scholar
  15. Petterborg LJ, Richardson BA, Vaughan MK, Reiter RJ (1984) Acute effects of a single afternoon melatonin injection on LH, prolactin and pineal melatonin titers in the Syrian hamster. J Neural Transm 59: 299–307Google Scholar
  16. Reiter RJ (1980) The pineal and its hormones in the control of reproduction in mammals. Endocrinol Rev 1: 109–131Google Scholar
  17. Reiter RJ (1984) Pineal indoles: production, secretion and actions. In: Muller EE, MacLeod RM (eds) Neuroendocrine perspectives, vol 3. Elsevier/North-Holland, pp 345–377Google Scholar
  18. Shah PN, Mhatre MC, Kothari LS (1984) Effect of melatonin on mammary carcinogenesis in intact and pinealectomized rats in varying photoperiods. Cancer Res 44: 3403–3407Google Scholar
  19. Sylvester PW, Aylsworth CF, Meites J (1981) Relationship of hormones to inhibition of mammary tumor development by underfeeding during the “critical period” after carcinogen administration. Cancer Res 41: 1384–1388Google Scholar
  20. Sylvester PW, Aylsworth CF, Van Vugt DA, Meites J (1982) Influence of underfeeding during the “critical period” or thereafter on carcinogeninduced mammary tumors in rats. Cancer Res 42: 4943–4947Google Scholar
  21. Tamarkin L, Reppert SM, Klein DC, Pratt B, Goldman BD (1980) Studies on the daily pattern of pineal melatonin in the Syrian hamster. Endocrinology 107: 1525–1529Google Scholar
  22. Tamarkin L, Cohen M, Roselle D, Reichert C, Lippman M, Chabner B (1981) Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz-(a)anthracene-induced mammary tumors in the rat. Cancer Res 41: 4432–4436Google Scholar
  23. Weindruch R, Walford RL (1982) Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. Science 215: 1415–1418Google Scholar
  24. Welsch CW, Nagasawa H (1977) Prolactin and murine mammary tumorigenesis: a review. Cancer Res 37: 951–963Google Scholar
  25. Willet WC, MacMahon (1984) Diet and cancer—an overview. New Engl J Med 310: 697–703Google Scholar
  26. Wurtman RJ, Moskowitz MA (1977) The pineal organ. N Engl J Med 296: 1329–1333Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • D. E. Blask
    • 1
  • S. M. Hill
    • 1
  • K. M. Orstead
    • 1
  • J. S. Massa
    • 1
  1. 1.Department of Anatomy, College of MedicineUniversity of ArizonaTucsonUSA

Personalised recommendations