Effect of a Short-Term and Long-Term Melatonin Administration on Mammary Carcinogenesis in Female Sprague-Dawley Rats Influenced by Repeated Psychoemotional Stress

Abstract

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 influenced by psychoemotional stress.