BACKGROUND: High levels of prostaglandins found in many neoplastic tissues, especially in colon cancer and breast cancer, suggest a role of cyclooxygenase in the process of carcinogenesis. MATERIAL AND METHODS: The aim of this study was to analyse the chemopreventive potential of non-steroidal inflammatory drug indomethacin and its combination with pineal hormone melatonin in rat mammary carcinogenesis induced by N-methyl-N-nitrosourea. Indomethacin was administered 3 times a week and melatonin 4 times a week, both substances in a concentration of 20 µg/ml of drinking water. Chemoprevention began approximately 2 weeks before carcinogen administration and lasted until the end of the experiment 25 weeks later. RESULTS: Indomethacin administered alone and in combination with melatonin stimulated the growth of mammary tumors. We found a significant increase in the average tumor volume caused by indomethacin alone by 126%, and in combination with melatonin by 104% compared to the control group. Indomethacin administered alone increased the incidence of tumors by 21.5% (also in combination with melatonin) and reduced the tumor latency by 17 days compared to controls. Melatonin alone significantly reduced tumor volume in comparison with control animals. During the long-term administration, both substances were well tolerated by animals. CONCLUSION: Indomethacin, a predominant cyclooxygenase inhibitor-1, showed significant neoplastic effects in the prevention of N-methyl-N-nitrosourea induced rat mammary carcinogenesis. This finding is in strong contrast to our previous experiment, where indomethacin in 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinogenesis revealed marked antineoplastic effects.
BACKGROUND: High levels of prostaglandins found in many neoplastic tissues, especially in colon cancer and breast cancer, suggest a role of cyclooxygenase in the process of carcinogenesis. MATERIAL AND METHODS: The aim of this study was to analyse the chemopreventive potential of non-steroidal inflammatory drug indomethacin and its combination with pineal hormone melatonin in rat mammary carcinogenesis induced by N-methyl-N-nitrosourea. Indomethacin was administered 3 times a week and melatonin 4 times a week, both substances in a concentration of 20 µg/ml of drinking water. Chemoprevention began approximately 2 weeks before carcinogen administration and lasted until the end of the experiment 25 weeks later. RESULTS:Indomethacin administered alone and in combination with melatonin stimulated the growth of mammary tumors. We found a significant increase in the average tumor volume caused by indomethacin alone by 126%, and in combination with melatonin by 104% compared to the control group. Indomethacin administered alone increased the incidence of tumors by 21.5% (also in combination with melatonin) and reduced the tumor latency by 17 days compared to controls. Melatonin alone significantly reduced tumor volume in comparison with control animals. During the long-term administration, both substances were well tolerated by animals. CONCLUSION:Indomethacin, a predominant cyclooxygenase inhibitor-1, showed significant neoplastic effects in the prevention of N-methyl-N-nitrosourea induced rat mammary carcinogenesis. This finding is in strong contrast to our previous experiment, where indomethacin in 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinogenesis revealed marked antineoplastic effects.