Preventive effect of indomethacin and melatonin on 7,12-dimethylbenz/a/anthracene-induced mammary carcinogenesis in female Sprague-Dawley rats. A preliminary report.

The aim of the experiment was to analyse the oncostatic effect of nonsteroi dal antiinflammatory drug INDO, hormone MEL and combination of both substan ces in DMBA-induced mammary carcinogenesis in female SD rats. Chemopreventi on started 10 days before the application of the first dose of DMBA to 35-d ay-old rats. INDO was administered in tap water (20 mug/ml of water) for 3 days in a week (days 2, 4 and 6), MEL solution in the concentration of 20 m ug/ml of tap water was administered between 3 p.m. and 8 a.m. for 4 days in a week (days 1, 3, 5 and 7); during other days the animals drank tap water only. In combined chemoprevention, rats were drinking solutions of INDO an d MEL according to the above-mentioned scheme. DMBA in the dose of 10 mg/ra t was administered intragastrically using a probe to all rats 3 times on po stnatal days 45, 50 and 55. There were four experimental groups: group 1 - without chemoprevention, group 2 - INDO treatment, group 3 - MEL treatment, group 4 - application of INDO + MEL. The experiment lasted 26 weeks from t he first administration of DMBA, when the final incidence and frequency of tumours per animal and group, as well as latency and average volume of tumo urs were evaluated. The content/concentration of malondialdehyde (MDA) was determined in selected tissues as a criterion of lipoperoxidation, consider ing its potential influencing by chemoprevention. The tumour incidence in controls was 100%; INDO reduced the incidence (36.8 4%) and frequency per group and animal, decreased the mean volume of tumour s and prolonged the latency. Chemoprevention using combination of INDO with MEL was successful like that with INDO; however, it did not influence the tumour volume. MEL decreased the incidence to 42.11% and pronouncedly reduc ed the tumour frequency per group. INDO, administered alone or in combinati on with MEL, reduced an increased content/concentration of MDA in the liver , bone marrow and serum of tumour-bearing rats. INDO, MEL and INDO + MEL ha d a pronounced chemopreventive effect and showed to be a favourable combina tion in prevention of experimental mammary carcinogenesis.