ABSTRACT
The purpose of this study was to evaluate the effect of genistein in nano, micro, and macro forms on the intensity of the DMBA-induced tumor process in rats and to understand the mechanisms of this action. The effect of genistein supplementation on the content of selected eicosanoids (HETEs, HODE, and HEPE) in the serum of rats was evaluated. The levels and expression of genes encoding various pro-inflammatory cytokines (IL-1, IL-6) and MMP-9 in the blood of rats were also investigated. The biological material for the study was blood obtained from female rats of the Sprague Dawley strain (n = 32). The animals were randomly divided into four groups: animals without supplementation, and animals supplemented at a dose of 0.2 mg/kg b.w. (0.1 mg/mL) with macro, micro (587 ± 83 nm), or nano (92 ± 41 nm) genistein. To induce mammary neoplasia (adenocarcinoma), rats were given 7,12-dimethyl-1,2-benz[a]anthracene (DMBA). The content of selected eicosanoids was determined by liquid chromatography with UV detection. An immunoenzymatic method was used to determine the content of cytokines and MMP-9. The expression of the IL-6, IL-1beta, and MMP-9 genes was determined with quantitative real-time PCR (qRT-PCR) using TaqMan probes. Based on the study, it was shown that supplementation of animals with genistein in macro, micro, and nano forms increased the intensity of the tumor process in rats. It was shown that the content of 12-HEPE, HODE, and 12-HETE in the serum of genistein-supplemented rats was statistically significantly lower with respect to the content of the aforementioned markers in the serum of rats receiving only a standard diet, devoid of supplementation. It was found that animals supplemented with nano-, micro-, and macrogenistein had higher levels of metalloproteinase-9, MMP-9, compared to animals without supplementation. There was a significant increase in MMP-9 gene expression in the blood of macrogenistein-supplemented animals, relative to the other groups of rats. On the basis of the study, it was shown that supplementation of animals with nano-, micro-, and macrogenistein had an effect on the development of the tumor process. Dietary supplementation with genistein significantly decreased the level of selected eicosanoids, which may have significant impacts on cancer development and progression.
ABSTRACT
The aim of this study was to assess the effect of genistein on the level of cholesterol, oxysterols, and composition of fatty acids, as well as enzymatic activity of desaturases, in rats with breast cancer. The animals were supplemented with nano-, micro-, and macrogenistein. Rats were treated with 7,12-dimethylbenz[a]anthracene to induce mammary adenocarcinoma. In the case of animals supplemented with genistein, an increase in the intensity of the carcinogenesis process was observed. Genistein supplementation also affected the cholesterol and oxysterols levels, as well as the composition of fatty acids, in the serum of rats with neoplastic disease. Dietary supplementation with nanogenistein significantly increased the level of cholesterol (p = 0.02) and cholesterol oxidation products (p = 0.02), which may have significant impacts on cancer development and progression.
ABSTRACT
BACKGROUND/AIM: The aim of the study was to assess the impact of nano-, micro-, and macro-sized-genistein on the growth and development of neoplasms in rats with mammary cancer. Additionally, the effect on the kinetics of changes (9-11-17-20 week of a rat's life) in the levels of methyl derivatives: 1-methyladenine, 3-methyladenine, 7-methylguanine, 1-methylguanine, 1-methyladenosine, 7-methylguanosine, O-methyl-guanosine and N6-methyl-2'-deoxyguanosine in the urine of rats was analyzed. MATERIALS AND METHODS: Female Sprague-Dawley rats divided into 4 groups were used in the study. Animals were fed only a control diet or diets supplemented with the nano-, micro- and macro-sized genistein. To induce the mammary adenocarcinoma, rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA). Modified nucleosides were determined by a high-performance liquid chromatography coupled to mass spectrometry method (LC-MS/MS). RESULTS: The supplementation of the diet of animals with genistein resulted in an increase in the excretion of methylated derivatives in the urine of rats. In the animals receiving standard diet, the levels of methyl derivatives increased during the study or remained relatively low. In the case of animals whose diet was supplemented with the various forms of genistein, the levels of methylated derivatives were very high from the beginning. CONCLUSION: High levels of methyl derivatives can influence carcinogenesis.
