Genotoxicity of Silver Nanoparticles in Vicia faba: A Pilot Study on the Environmental Monitoring of Nanoparticles

The use of silver nanoparticles (AgNPs) in commercial products has increased significantly in recent years. Although there have been some attempts to determine the toxic effects of AgNPs in mammalian and human cell-lines, there is little information on plants which play a vital role in ecosystems. The study reports the use of Vicia faba root-tip meristem to investigate the genotoxicity of AgNPs under modified GENE-TOX test conditions. The root tip cells of V. faba were treated with four different concentrations of engineered AgNPs dispersion to study toxicological endpoints such as mitotic index (MI), chromosomal aberrations (CA) and micronucleus induction (MN). For each concentration, five sets of microscopy observations were carried out. The results demonstrated that AgNPs exposure significantly increased (p < 0.05) the number of chromosomal aberrations, micronuclei, and decreased the MI in exposed groups compared to control. From this study we infer that AgNPs might have penetrated the plant system and may have impaired mitosis causing CA and MN. The results of this study demonstrate that AgNPs are genotoxic to plant cells. Since plant assays have been integrated as a genotoxicity component in risk assessment for detection of environmental mutagens, they should be given full consideration when evaluating the overall toxicological impact of the nanoparticles in the environment

Environmental Exposure and Health Effects Associated with Malathion Toxicity

Malathion (O,O-dimethyl-S-1,2-bis ethoxy carbonyl ethyl phosphorodithionate) is a non-systemic, wide-spectrum pesticide. It is widely used throughout the world for agricultural, residential, and public health purposes, mainly to enhance food production and to provide protection from disease vectors. Malathion preference over other organophosphate pesticides relates to its low persistence in the environment as it is highly susceptible to hydrolysis, photolysis, and biodegradation. However, numerous malathion poisoning incidents including acute and chronic cases have been reported among pesticide workers and small children through accidental exposure. Malathion toxicity is compounded by its reactive metabolites and also depends upon the product purity, route of exposure, nutritional status, and gender of exposed individuals. Its metabolic oxidation in mammals, insects, and plants leads to the formation of malaoxon which appears to be several times more acutely toxic and represents the primary cause of malathion’s toxicity. Depending on the level of exposure, several signs and symptoms of toxicity including numbness, tingling sensation, headache, dizziness, difficulty breathing, weakness, irritation of skin, exacerbation of asthma, abdominal cramps, and death have been reported. Similar to other organophosphate pesticides, malathion exerts it toxic action by binding to acetylcholinesterase enzyme and inhibiting its activity, leading to accumulation of acetylcholine in synaptic junctions, which in turn results in overstimulation of cholinergic, muscarinic, and nicotinic receptors, and subsequent induction of adverse biologic effects. This chapter provides an update and analysis of the production and use, environmental occurrence, molecular mechanisms of toxicity, genotoxicity and carcinogenicity, and adverse human health effects associated with malathion exposure

Ameliorative Effects of Dimetylthiourea and N-Acetylcysteine on Nanoparticles Induced Cyto-Genotoxicity in Human Lung Cancer Cells-A549

We study the ameliorative potential of dimetylthiourea (DMTU), an OH• radical trapper and N-acetylcysteine (NAC), a glutathione precursor/H2O2 scavenger against titanium dioxide nanoparticles (TiO2-NPs) and multi-walled carbon nanotubes (MWCNTs) induced cyto-genotoxicity in cultured human lung cancer cells-A549. Cytogenotoxicity was induced by exposing the cells to selected concentrations (10 and 50 µg/ml) of either of TiO2-NPs or MWCNTs for 24 h. Anti-cytogenotoxicity effects of DMTU and NAC were studied in two groups, i.e., treatment of 30 minutes prior to toxic insult (short term exposure), while the other group received DMTU and NAC treatment during nanoparticles exposure, i.e., 24 h (long term exposure). Investigations were carried out for cell viability, generation of reactive oxygen species (ROS), micronuclei (MN), and expression of markers of oxidative stress (HSP27, CYP2E1), genotoxicity (P53) and CYP2E1 dependent n- nitrosodimethylamine-demethylase (NDMA-d) activity. In general, the treatment of both DMTU and NAC was found to be effective significantly against TiO2-NPs and MWCNTs induced cytogenotoxicity in A549 cells. Long-term treatment of DMTU and NAC during toxic insults has shown better prevention than short-term pretreatment. Although, cells responded significantly to both DMTU and NAC, but responses were chemical specific. In part, TiO2-NPs induced toxic responses were mediated through OH• radicals generation and reduction in the antioxidant defense system. While in the case of MWCNTs, adverse effects were primarily due to altering/hampering the enzymatic antioxidant system. Data indicate the applicability of human lung cancer cells-A549 as a pre-screening tool to identify the target specific prophylactic and therapeutic potential of drugs candidate molecules against nanoparticles induced cellular damages

The Effects of Arsenic Trioxide on DNA Synthesis and Genotoxicity in Human Colon Cancer Cells

Colon cancer is the third leading cause of cancer-related deaths worldwide. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic in human colon cancer (HT-29), lung (A549) and breast (MCF-7) carcinoma cells. The purpose of the present study is to investigate the effects of arsenic trioxide on DNA synthesis and the possible genotoxic effects on human colon cancer cells. HT-29 cells were cultured according to standard protocol, followed by exposure to various doses (0, 2, 4, 6, 8, 10, and 12 μg/mL) of arsenic trioxide for 24 h. The proliferative response (DNA synthesis) to arsenic trioxide was assessed by [3H]thymidine incorporation. The genotoxic effects of arsenic-induced DNA damage in a human colon cancer cell line was evaluated by the alkaline single cell gel electrophoresis. Results indicated that arsenic trioxide affected DNA synthesis in HT-29 cells in a biphasic manner; showing a slight but not significant increase in cell proliferation at lower levels of exposure (2, 4 and 6 μg/mL) followed by a significant inhibition of cell proliferation at higher doses (i.e., 8 and 10 μg/mL). The study also confirmed that arsenic trioxide exposure caused genotoxicity as revealed by the significant increase in DNA damage, comet tail-lengths, and tail moment when compared to non-exposed cells. Results of the [3H]thymidine incorporation assay and comet assay revealed that exposure to arsenic trioxide affected DNA synthesis and exhibited genotoxic effects in human colon cancer cells

Antitumor Activity of Noscapine in Combination with Doxorubicin in Triple Negative Breast Cancer

The aim of this study was to investigate the anticancer activity and mechanism of action of Noscapine alone and in combination with Doxorubicin against triple negative breast cancer (TNBC).TNBC cells were pretreated with Noscapine or Doxorubicin or combination and combination index values were calculated using isobolographic method. Apoptosis was assessed by TUNEL staining. Female athymic Nu/nu mice were xenografted with MDA-MB-231 cells and the efficacy of Noscapine, Doxorubicin and combination was determined. Protein expression, immunohistochemical staining were evaluated in harvested tumor tissues. values of 36.16±3.76 and 42.7±4.3 µM respectively. The CI values (<0.59) were suggestive of strong synergistic interaction between Noscapine and Doxorubicin and combination treatment showed significant increase in apoptotic cells. Noscapine showed dose dependent reduction in the tumor volumes at a dose of 150–550 mg/kg/day compared to controls. Noscapine (300 mg/kg), Doxorubicin (1.5 mg/kg) and combination treatment reduced tumor volume by 39.4±5.8, 34.2±5.7 and 82.9±4.5 percent respectively and showed decreased expression of NF-KB pathway proteins, VEGF, cell survival, and increased expression of apoptotic and growth inhibitory proteins compared to single-agent treatment and control groups.Noscapine potentiated the anticancer activity of Doxorubicin in a synergistic manner against TNBC tumors via inactivation of NF-KB and anti-angiogenic pathways while stimulating apoptosis. These findings suggest potential benefit for use of oral Noscapine and Doxorubicin combination therapy for treatment of more aggressive TNBC