Abstract
Abstract The aim of the research was to compare the impact of nano- and micro-sized-zinc on the kinetics of changes in the level of 3-methyladenine, 7-methylguanine, 7-methylguanosine, O-methylguanosine, 1-methyladenosine, N6-methyl-2’-deoxyguanosine in urine of rats with breast cancer. Female Sprague-Dawley rats divided into 3 groups were used in the study. Animals were fed only a control diet or diets supplemented with the nano and micro-sized zinc particles. To induce the mammary cancer (adenocarcinoma), rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA). Modified nucleosides were determined by a validated high performance liquid chromatography coupled to mass spectrometry method. In the first stage of investigations a synergistic activity of nanosized Zn with DMBA on the growth of the neoplastic process was found. During that time a statistically significant increase in the levels of all six examined markers in the rats’ urine was observed. However, as the experiment continued, the supplementation with nanosized zinc caused inhibition of tumour growth, being followed by regression and remission of tumours, as well as, a statistically significant systematic reduction of the levels of methyl derivatives in the urine. Biopsy images indicated grade 1 tumours with multiple inflammatory infiltrates in the group treated with zinc nanoparticles, whereas, in the other groups, moderately-differentiated grade 2 adenocarcinoma was identified. It was found that the biological activity of zinc depends on the size of applied particles, as the treatment with zinc microparticles has not had much effect on cancer progression.
Highlights
Recent studies have shown a potential role of using nanoparticles of zinc in biomedicine and therapeutics
Moghaddam et al [1] demonstrated that the possibility of using zinc nanoparticles in treatment of MCF-7 breast cancer and excessive reactive oxygen species (ROS) generation caused upregulation of the pro-apoptotic p53, p21, Bax, and JNK genes, whereas anti-apoptotic genes Bcl-2, AKT1, and ERK1/2 were downregulated in a dose-dependent manner
In the case of rats that were not supplemented and obtained a standard diet the incidence of cancer was 100%, the weight of tumours was in the range 0.1–7.8 g and the number of tumours per rat ranged from 2 to 9 (4.63 ± 2.39) (Table 2)
Summary
Recent studies have shown a potential role of using nanoparticles of zinc in biomedicine and therapeutics. Excessive ROS generation which, if effectively targeted at the cancer cells, will lead to their selective destruction. This mechanism was confirmed in several experiments using laboratory animals [15,16,17]. Recent studies have highlighted the application of the combination of the autophagy inhibitor 3-methyladenine and radiochemotherapy in the diagnosis and treatment of cancer. This combination is known to effectively reduce the proliferation and induce apoptosis of cancer cells [18,19,20]. Especially on physicochemical properties of nanoparticles, their behaviour in environments of cancer and their interaction with the biological system
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