Relative Genotoxicities of PAH of Molecular Weight 252 AMU in Coal Tar-Contaminated Sediment

Bioassay-directed chemical fractionation methodology was used to calculate relative mutagenic potencies of polycyclic aromatic hydrocarbons (PAH) of molecular weight 252 amu in coal tarcontaminated sediment from Sydney Harbour, Nova Scotia. A normal phase HPLC technique was used to separate organic solvent extracts into fractions containing isomeric PAH of a single benzologue class. Bioassays with Salmonella typhimurium strain YG1025 with the addition of oxidative metabolism (S9) showed that approximately 50% of the mutagenic activity observed in the sediment extract was associated with PAH of molecular weight 252 amu. Further separation of the 252 PAH fraction using reversed phase HPLC yielded subfractions containing individual compounds; bioassay dose-response curves for these subfractions showed that benzo[a]pyrene was responsible for approximately 75% of the activity of the 252 PAH fraction.     

紫色杆菌素及脱氧紫色杆菌素的基因毒性评价

目的：考察紫色杆菌素、脱氧紫色杆菌素以及二者混合物的基因毒性,为其更广泛的活性研究和应用奠定基础。方法：利用SOS/umu检测试剂盒定量分析紫色杆菌素、脱氧紫色杆菌素、二者混合物以及各自的S9代谢产物是否刺激鼠伤寒沙门菌Salmonella typhimurium NM2009细胞产生了SOS修复,以及与阳性药物2-氨基芴（2-aminofluorene,AF-2）和2-氨基蒽（2-aminoanthracene,2-AA）进行对比所产生毒性作用的强弱。结果：32.6 μg/mL的脱氧紫色杆菌素、经S9代谢后的34.2 μg/mL的紫色杆菌素和33.4 μg/mL的混合物对S. typhimurium NM2009细胞产生了基因毒性,但与阳性对照物相比属于低毒性物质,且相同剂量的紫色杆菌素和脱氧紫色杆菌素以及二者混合物的基因毒性基本相同,二者混合后未产生协同效应。结论：紫色杆菌素和脱氧紫色杆菌素属于低基因毒性物质。     

Looking for the LOAEL or NOAEL Concentration of Nickel-Oxide Nanoparticles in a Long-Term Inhalation Exposure of Rats

Rats were exposed to nickel oxide nano-aerosol at a concentration of 2.4 ± 0.4 µg/m³ in a “nose only” inhalation setup for 4 h at a time, 5 times a week, during an overall period of 2 weeks to 6 months. Based on the majority of the effects assessed, this kind of exposure may be considered as close to LOAEL (lowest observed adverse effect level), or even to NOAEL (no observed adverse effect level). At the same time, the experiment revealed genotoxic and allergic effects as early as in the first weeks of exposure, suggesting that these effects may have no threshold at all.     

Impact of consumption of repeatedly heated cooking oils on the incidence of various cancers- A critical review

Repeated heating of vegetable oils at high temperatures during cooking is a very common cooking practice. Repeatedly heated cooking oils (RCO) can generate varieties of compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have been reported as carcinogenic. RCO is one of the commonly consumed cooking and frying medium. These RCO consumption and inhalation of cooking fumes can pose a serious health hazard. Taking into account exploratory study, the present review aims to provide the consumption of RCO and its fumes cause the high incidence of genotoxic, mutagenic, tumorogenic and various cancers. The information on RCO and its fumes were collected through a library database and electronic search (ScienceDirect, PubMed, and Google Scholar). Remarkable studies demonstrated that the health adverse effects of RCO and its cooking fumes have been often attributed to their detrimental properties and ease to genotoxic, mutagenic and carcinogenic activities. RCO and its cooking fumes were found to enhance the incidence of aberrant cells, including breaks, fragments, exchanges and multiple chromosomal damages and micronuclei in a dose-dependent manner. Furthermore, the large consumption of RCO has been associated with a number of malignancies, including lung, colorectal, breast, and prostate cancers. The present review provides additional insights into the polluting features of PAHs produced various cancers via cooking activities in indoor environments.     

Antigenotoxicity of extracts from Pleurotus citrinopileatus

While Pleurotus citrinopileatus is a widely used edible mushroom, little is known about its physiological effects. Extracts, including aqueous extract, water‐soluble polysaccharide (WSP), crude protein solution (CPS) and residue from chloroform–ethyl acetate–methanol elution (CEM), were obtained first from fruiting bodies, through a solid‐state culture, and then from the mycelium, through a submerged culture. This study explored the antigenotoxicity effects of these extracts from Pleurotus citrinopileatus via the Ames test and a spore rec‐Assay. The results showed that, regardless of where the extract came from, the fruiting body or the mycelium, the antigenotoxicity effect was highest for CEM, followed by CPS, aqueous extract and WSP. The results of the Ames test indicated that, among several mutagens, CEM had the highest inhibition rate against AFB_l in TA98 and TA100 and the lowest inhibition rate against NQNO. The concentrations of the various extracts were as follows: water extracts were 1 mg ml^?1 and 5 mg ml^?1 WSP, while CPS and CEM were 0.4 mg ml^?1 and 2 mg ml^?1, respectively; the higher the concentration of the extract, the higher the antimutagenicity effect. The results of the rec‐Assay indicated that CEM had the highest anti‐DNA‐damaging activity with or without the S9 mixture; the higher the concentration, the more significant the effect (p < 0.05). The anti‐DNA‐damaging activities were lower in the water extract concentrations, at 30 µg disc^?1 dry weight^?1, while the WSP, CPS and CEM at 12, 150 and 60 µg disc^?1, respectively, were high. Copyright © 2004 Society of Chemical Industry     

Antioxidant and toxicity tests of roasted noni (Morinda citrifolia) leaf infusion

The antioxidant properties and toxicity profile of roasted noni ( Morinda citrifolia L . ) leaf infusion were evaluated. The 2,2-diphenylpicrylhydrazyl (DPPH) radical scavenging activity was greater than green tea infusion (81.6 ± 0.9% vs. 57.5 ± 1.8%, P  < 0.001). The mean quercetin and kaempferol contents of roasted noni leaf infusion, as prepared by the consumer, were 0.24 ± 0.01 and 0.14 ± 0.01 μg mL⁻¹, respectively. Tannic acid content was 10 ± 1 μg mL⁻¹. The infusion was non-mutagenic in the reverse mutation test in Salmonella typhimurium and did not induce primary DNA damage in E. coli PQ37. Further, no significant primary DNA damage was induced by 5,15-dimethylmorindol, which was the only detectable anthraquinone in noni leaves. The infusion was not cytotoxic in the 24 h brine shrimp toxicity test (LC₅₀ > 1 mg mL⁻¹), nor was there any evidence of acute oral toxicity from the freeze–dried infusion in Sprague–Dawley rats (LD₅₀ > 2000 mg kg⁻¹ b.w.).     

1,4-Naphthoquinone (CNN1) Induces Apoptosis through DNA Damage and Promotes Upregulation of H2AFX in Leukemia Multidrug Resistant Cell Line

The multidrug resistance (MDR) phenotype is one of the major obstacles in the treatment of chronic myeloid leukemia (CML) in advantage stages such as blast crisis. In this scenario, more patients develop resistance mechanisms during the course of the disease, making tyrosine kinase inhibitors (TKIs) target therapies ineffective. Therefore, the aim of the study was to examine the pharmacological role of CNN1, a para-naphthoquinone, in a leukemia multidrug resistant cell line. First, the in vitro cytotoxic activity of Imatinib Mesylate (IM) in K-562 and FEPS cell lines was evaluated. Subsequently, membrane integrity and mitochondrial membrane potential assays were performed to assess the cytotoxic effects of CNN1 in K-562 and FEPS cell lines, followed by cell cycle, alkaline comet assay and annexin V-Alexa Fluor^® 488/propidium iodide assays (Annexin/PI) using flow cytometry. RT-qPCR was used to evaluate the H2AFX gene expression. The results demonstrate that CNN1 was able to induce apoptosis, cell membrane rupture and mitochondrial membrane depolarization in leukemia cell lines. In addition, CNN1 also induced genotoxic effects and caused DNA fragmentation, cell cycle arrest at the G2/M phase in leukemia cells. No genotoxicity was observed on peripheral blood mononuclear cells (PBMC). Additionally, CNN1 increased mRNA levels of H2AFX. Therefore, CNN1 presented anticancer properties against leukemia multidrug resistant cell line being a potential anticancer agent for the treatment of resistant CML.     

Genotoxicological Characterization of (±)cis-4,4′-DMAR and (±)trans-4,4′-DMAR and Their Association

The novel psychoactive substance (NPS) 4-Methyl-5-(4-methylphenyl)-4,5-dihydroxazol-2-amine (4,4′-DMAR) shows psychostimulant activity. Data on the acute toxicity of 4,4′-DMAR are becoming increasingly available, yet the long-term effects are still almost unknown. In particular, no data on genotoxicity are available. Therefore, the aim of the present study was to evaluate its genotoxic potential using the “In Vitro Mammalian Cell Micronucleus Test” (MNvit) on (±)cis-4,4′-DMAR and (±)trans-4,4′-DMAR and their associations. The analyses were conducted in vitro on human TK6 cells. To select suitable concentrations for MNvit, we preliminarily evaluated cytotoxicity and apoptosis. All endpoints were analysed by flow cytometry. The results reveal the two racemates’ opposite behaviours: (±)cis-4,4′-DMAR shows a statistically significant increase in micronuclei (MNi) frequency that (±)trans-4,4′-DMAR is completely incapable of. This contrast confirms the well-known possibility of observing opposite biological effects of the cis- and trans- isomers of a compound, and it highlights the importance of testing single NPSs that show even small differences in structure or conformation. The genotoxic capacity demonstrated stresses an additional alarming toxicological concern related to this NPS. Moreover, the co-treatments indicate that consuming both racemates will magnify the genotoxic effect, an aspect to consider given the unpredictability of illicit drug composition.     

两色金鸡菊的遗传毒性及其食用安全性评价

目的 检测两色金鸡菊的遗传毒性,为其食用安全性评价提供研究数据。方法 以两色金鸡菊(水提取物)为受试物,采用细菌回复突变试验、小鼠淋巴瘤细胞TK基因突变试验(MLA)分别在代谢活化(+S9)和非代谢活化(-S9)条件下检测;以两色金鸡菊(粉末)为受试物,采用小鼠骨髓微核试验检测。细菌回复突变试验采用平板掺入法,检测1.25、2.5、5、10 mg/皿4个剂量诱发鼠伤寒沙门氏菌TA98、TA100、TA1535、TA1537及大肠杆菌WP2uvr A的his^-/trp^-回复突变能力;MLA采用微孔法,检测1.5、2.0、2.5、3.0、3.5 mg/mL 5个浓度在±S9/3 h处理条件下是否诱发L5178Y细胞tk^+/-基因突变频率(MF)增加,评价对测试细胞的损伤作用;小鼠骨髓微核试验：间隔24h连续3次经口灌胃给予CD-1小鼠900、1800、3600 mg/kg两色金鸡菊粉末(200目),并在末次给予后18～24 h取材,计数2000个嗜多染红细胞中含微核细胞,计算微核细胞率。结果 +、-S9条件下,1.25～10...     

Cyto-Genotoxic and Transcriptomic Alterations in Human Liver Cells by Tris (2-Ethylhexyl) Phosphate (TEHP): A Putative Hepatocarcinogen

Tris (2-ethylhexyl) phosphate (TEHP) is an organophosphate flame retardant (OPFRs) which is extensively used as a plasticizer and has been detected in human body fluids. Contemporarily, toxicological studies on TEHP in human cells are very limited and there are few studies on its genotoxicity and cell death mechanism in human liver cells (HepG2). Herein, we find that HepG2 cells exposed to TEHP (100, 200, 400 µM) for 72 h reduced cell survival to 19.68%, 49.83%, 58.91% and 29.08%, 47.7% and 57.90%, measured by MTT and NRU assays. TEHP did not induce cytotoxicity at lower concentrations (5, 10, 25, 50 µM) after 24 h and 48 h of exposure. Flow cytometric analysis of TEHP-treated cells elevated intracellular reactive oxygen species (ROS), nitric oxide (NO), Ca⁺⁺ influx and esterase levels, leading to mitochondrial dysfunction (ΔΨm). DNA damage analysis by comet assay showed 4.67, 9.35, 13.78-fold greater OTM values in TEHP (100, 200, 400 µM)-treated cells. Cell cycle analysis exhibited 23.1%, 29.6%, and 50.8% of cells in SubG1 apoptotic phase after TEHP (100, 200 and 400 μM) treatment. Immunofluorescence data affirmed the activation of P53, caspase 3 and 9 proteins in TEHP-treated cells. In qPCR array of 84 genes, HepG2 cells treated with TEHP (100 µM, 72 h) upregulated 10 genes and downregulated 4 genes belonging to a human cancer pathway. Our novel data categorically indicate that TEHP is an oxidative stressor and carcinogenic entity, which exaggerates mitochondrial functions to induce cyto- and genotoxicity and cell death, implying its hepatotoxic features.