251 NEOPLASMA 54, 3, 2007 Effect of prolonged psychoemotional stress and melatonin on experimental mammary carcinogenesis in female rats M. KASSAYOVÁ*, L. FRIEDMANOVÁ, P. ORENDÁŠ, P. KUBATKA 1 , B. BOJKOVÁ, N. BOBROV 2 , E. AHLERSOVÁ, I. AHLERS Department of Animal Physiology, Institute of Biological and Ecological Sciences, P.J. Šafárik University – Faculty of Science, Moyzesova 11, 040 01 Košice, e-mail: monika.kassayova@upjs.sk; 1 Institute of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Záborského 2, 036 45 Martin; 2 Institute of Forensic Medicine, P.J. Šafárik University – Faculty of Medicine, Šrobárova 2, 040 01 Košice Received October 20, 2006 The aim of the present study was to determine whether prolonged stress – repeated immobilization in boxes during the period of 18 weeks (IMS) influenced development and progression of N-methyl-N-nitrosourea (NMU)-induced mammary tumors in female Sprague-Dawley rats and whether long-term MEL application affected changes caused by stress. NMU was applied intraperitoneally in two doses each of 50 mg/kg b.w. between 40 – 50 postnatal days. Melatonin (MEL) was administered in drinking water in a concentration of 4 µg/ml (daily from 3 p.m to 8 a.m), application was initiated 3 days prior to first NMU dose and lasted until the end of the experiment. Immobilization (2 h/day) began on the fifth day after second carcinogen application, animals were immobilized three times a week. Repeated immobilization of rats during 18 weeks decreased tumor frequency per group and per animal by 30% and tumor volume gain by 16% as opposed to control (NMU) animals. Combination of repeated immobilization and a long-term MEL application lowered incidence by 13% when compared to control, prolonged latency by 13%, decreased tumor frequency per group (by 44%) and per animal (by 35%). Tumor volume gain increased by 35% but their cumulative volume prominently decreased by 74% as opposed to control. Tumor volume was the most markedly influenced by MEL, induced tumors developed more rapidly – tumor volume gain increased by 61%. However, their cumulative volume markedly decreased by 75% when compared to immobilized group drinking water. Prolonged stress inhibited development and progression of NMU-induced mammary gland tumors in female rats and this effect was enhanced by long-term melatonin administration. Key words: prolonged immobilization stress, mammary carcinogenesis, melatonin, rat * Corresponding author Breast cancer is the most frequently occurred tumor in women. According to International Agency for Research on Cancer 1.2 million new cases were diagnosed in 2002 and more than 400 000 women died of breast cancer [1]. Several biological factors have been identified representing risk in breast cancer etiology and these are related to life style, e.g. dietary fat intake, alcohol consumption, physical activity. The role of psychosocial factors has not been sufficiently ex- plained. Although a great number of studies investigating the effect of psychoemotional stress on development and progres- sion of mammary tumors in humans appear annually, their results are inconsistent due to certain degree of subjectivity associated with filling in questionnaires, which are fundamen- tal for these studies as well as objectionable proof of direct causal relation between stress and cancer development. In connection with the aforementioned experimental animal models the studies carried out under controlled conditions, with exactly defined kind, duration and intensity of stressor are expected to reveal more valuable results [2]. Melatonin, a pineal gland hormone, displays a wide range of beneficial effects in organism; its receptors were described in numerous peripheral tissues. Melatonin synthesis has been proved, apart from pineal gland, in gastrointestinal tract, Harderian glands, retina, gonads and other organs. MEL has also been shown to have immunostimulating and tumorsuppressive effect [3]. The aim of our study was to determine the extent to what prolonged stress – repeated immobilization in boxes influ- ences development and progression of chemically induced mammary tumors in female rats and the effect of long-term MEL application on stress-induced changes.