Abstract
BackroundThe aim of the present study was to assess the effect of dietary supplementation (copper or copper and resveratrol) on the intensity of carcinogenesis and the frequency of microsatellite instability in a widely used model of mammary carcinogenesis induced in the rat by treatment with 7,12-dimethylbenz[a]anthracene (DMBA).MethodsDNA was extracted from rat mammary cancers and normal tisues, amplified by PCR, using different polymorphic DNA markers and the reaction products were analyzed for microsatellite instability.ResultsIt was found that irrespectively of the applied diet there was no inhibition of mammary carcinogenesis in the rats due to DMBA. Besides, in the groups supplemented with Cu (II) or Cu (II) and resveratrol the tumor formation was clearly accelerated. Unlike the animals that were fed with standard diet, the supplemented rats were characterized by the loss of heterozygosity of microsatellite D3Mgh9 in cancer tumors (by respectively 50 and 40%). When the animals received Cu (II) and resveratrol supplemented diet the occurrence of genomic instability was additionally found in their livers in the case of microsatellite D1Mgh6 (which was stable in the animals without dietary supplementation).ConclusionsIdentification of the underlying mechanisms by which dietary factors affect genomic stability might prove useful in the treatment of mammary cancer as well as in the incorporation of dietary factors into mammary cancer prevention strategies.
Highlights
Polyphenolic compounds have been already shown to be chemopreventive against various stages of chemically induced carcinogenesis [1,2]
The aim of the present study was to assess the effect of dietary supplementation on the intensity of carcinogenesis and the frequency of microsatellite instability in a widely used model of mammary carcinogenesis induced in the rat by treatment with 7,12-dimethylbenz[a]anthracene
Of the diet applied the effectiveness of cancer induction by DMBA was 100%
Summary
Polyphenolic compounds have been already shown to be chemopreventive against various stages of chemically induced carcinogenesis [1,2]. The procancerogenic activity of copper was found to be related to the formation of reactive oxygen radicals that impair DNA threads and to initiation of angiogenesis of the tumor [3]. Many investigations were performed that confirmed the effectiveness of using copper chelators (e.g. penicillamines, tetrathiomolybdate, zinc anions) as anticancer agents [4,5]. In this research resveratrol was used as the copper chelator because this compound occurs in nature and exhibits strong anti-oxidative properties [2]. The hydroxyl groups of polyphenols, when reacting with free radicals, form more stable complexes.
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