The aim of this study was to evaluate the effect of melatonin (MEL) on N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in female Sprague-Dawley rats exposed to repeated psychoemotional stress -immobilization in boxes. NMU was applied intraperitoneally in two doses each of 50 mg/kg b.w. between 40 -50 postnatal days. Melatonin was administered in drinking water at a concentration of 4 μg/ml daily from 15:00 h to 8:00 h. The application was initiated 5 days prior to the fi rst NMU dose and lasted 15 days, i.e. during the promotion phase of tumour development, or long-term until the end of the experiment (week 20). Immobilization (2 h per day) began on the third day after the second carcinogen application and lasted for 7 consecutive days.Short-term MEL administration to immobilized animals increased incidence by 22%, decreased tumour frequency per animal by 26% and reduced tumour volume gain (by 21%) when compared to the immobilized group without MEL application. Decreased frequency per animal by 28% and more than a 40% decrease in tumour volume gain and cumulative volume were the most pronounced changes in the animals drinking MEL until the end of the experiment.Long-term MEL administration reduced the number and size of mammary tumours more markedly than its short-term administration. Melatonin decreased certain attributes of mammary carcinogenesis in female rats infl uenced by psychoemotional stress.
Melatonin, mammary carcinogenesis, psychoemotional stress -restraint, ratBreast cancer is the most frequently diagnosed tumour in women world-wide. In most European countries the incidence is increasing; 350 000 new cases are recorded annually and annual mortality rate is 130 000 (Tyczynski et al. 2004). Chemically induced mammary carcinogenesis in rats is a widely used model to study preventive and therapeutic effects of various substances on tumour development. Melatonin (MEL) has been one of the most discussed substances since the 1970's. Melatonin is an endogenous pineal gland hormone and its oncostatic properties were proved mainly in hormone-sensitive mammary tumour in vivo and in vitro.Tumour-suppressive effects of MEL are exerted by different mechanisms of action. Indirect effect of MEL is produced through its inhibition of the activity of neuroendocrinereproductive axis with a consequent decrease in circulating levels of hormones that stimulate mammary tissue proliferation, mainly estrogens and prolactin (Tamarkin et al. 1981). MEL is capable of direct interaction with estrogen receptors resulting in their expression decrease and modulation of estrogen signal transfer