Recent Trends in Rapid Environmental Monitoring of Pathogens and Toxicants: Potential of Nanoparticle-Based Biosensor and Applications

Koedrith, Preeyaporn,Thasiphu, Thalisa,Weon, Jong-Il,Boonprasert, Rattana,Tuitemwong, Kooranee,Tuitemwong, Pravate Hindawi Publishing Corporation 2015 The Scientific World Journal Vol.2015 No.-

<P>Of global concern, environmental pollution adversely affects human health and socioeconomic development. The presence of environmental contaminants, especially bacterial, viral, and parasitic pathogens and their toxins as well as chemical substances, poses serious public health concerns. Nanoparticle-based biosensors are considered as potential tools for rapid, specific, and highly sensitive detection of the analyte of interest (both biotic and abiotic contaminants). In particular, there are several limitations of conventional detection methods for water-borne pathogens due to low concentrations and interference with various enzymatic inhibitors in the environmental samples. The increase of cells to detection levels requires long incubation time. This review describes current state of biosensor nanotechnology, the advantage over conventional detection methods, and the challenges due to testing of environmental samples. The major approach is to use nanoparticles as signal reporter to increase output rather than spending time to increase cell concentrations. Trends in future development of novel detection devices and their advantages over other environmental monitoring methodologies are also discussed.</P>

Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

Koedrith, Preeyaporn,Seo, Young Rok Molecular Diversity Preservation International (MD 2011 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.12 No.12

<P>Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression.</P>

Recent toxicological investigations of metal or metal oxide nanoparticles in mammalian models in vitro and in vivo: DNA damaging potential, and relevant physicochemical characteristics

Koedrith, Preeyaporn,Boonprasert, Rattana,Kwon, Jee Young,Kim, Im-Soon,Seo, Young Rok THE KOREAN SOCIETY OF TOXICOGENOMICS AND TOXICOPRP 2014 MOLECULAR AND CELLULAR TOXICOLOGY Vol.10 No.2

Concomitant with the increase in production and application of various nanomaterials, researches on their cytotoxic and genotoxic potential have become well established, as exposure to these nanoscaled materials may contribute to detrimental health effects. Positive indications of the damaging effects of nanoparticles on DNA are likely to be inconsistent in in vitro systems, and thus the implementation of in vivo investigations has been achieved. This review summarizes the current results, both in vitro and in vivo, of the genotoxic effects of potential metal or metal oxide nanoparticles, including the oxides of aluminium, iron, silica, titanium, and zinc, as well as silver, gold, cobalt, quantum dots, and so forth. They present indications of different types of DNA damage, ranging from chromosomal aberrations, through DNA strand breaks, oxidative DNA damage, to mutations. Their toxicological profiles are definitely associated with physicochemical characters, depending upon the characterization methods by which they are analyzed, in particular, microscopy techniques. Besides physicochemical properties, we also discuss significant parameters that may influence genotoxic response, including toxicity assays/endpoint tests, exposure duration and route of exposure, and experimental conditions. We describe advantages and disadvantages of particular characterization methods, as well as the appropriateness of methodologies for investigating physicochemical characters. Therefore, recommendations on particle characterization are further emphasized, to provide better understanding of genotoxic potential.

Induction of doxorubicin-mediated apoptosis via thioredoxin reductase 1 RNAi in human colon cancer cells

Koedrith, Preeyaporn,Seo, Young-Rok THE KOREAN SOCIETY OF TOXICOGENOMICS AND TOXICOPRP 2011 MOLECULAR AND CELLULAR TOXICOLOGY Vol. No.

In mammals, thioredoxin reductase 1 (Trr1) is of potential importance in defense against oxidative stress and regulation of redox homeostasis. Nevertheless, overexpression of this selenoprotein Trr1 is also manifested in several types of malignant cancers, leading to hypothesis that Trr1 might be a molecular candidate for anticancer drug treatment. An anthracycline antibiotic, doxorubicin (DOX), has been extensively applied in the chemotherapy of solid tumor tissues including colon. Cytotoxification of DOX is targeting on damage to DNA molecules via possible generation of reactive oxygen species (ROS) with consequent inhibition of macromolecule biosynthesis. At present work focusing on specific Trr1 knockdown using short hairpin RNA (shRNA) based viral vector, the important role of Trr1 on DOX resistance in human colon cancer RKO cell was deliberately investigated. Intriguingly, our finding presented that the stable Trr1 shRNA knockdown had higher sensitivity to DOX relative to the wild type. With respect to this point, accumulated intracellular ROS was notably stimulated in the Trr1 shRNA defect rather than the wild type. Apparently, it was also direct linkage between ROS level and extent of phosphorylated histone "gamma-H2AX", indicative of DNA damage. Strikingly, our important observation revealed that in presence of DOX Trr1 deficiency probably accelerated double strand breaks to DNA, provided evidence as neutral comet assay. Additionally, our data demonstrated that DOX-induced apoptosis was also correlated with increment of oxygen radicals damage to DNA. Taken together, it was worthy to conclude that specific reduction of Trr1 expression via shRNA based interference might be a considerable molecular approach to improve effectiveness of DOX-mediated killing in treatment of human colon cancer cells, through stimulation of oxidative insult. This implied that Trr1 might be a plausible target in cancer therapy.

Enhancement of the efficacy of mitomycin C-mediated apoptosis in human colon cancer cells with RNAi-based thioredoxin reductase 1 deficiency

KOEDRITH, PREEYAPORN,SEO, YOUNG ROK Spandidos Publications 2011 Experimental and therapeutic medicine Vol.2 No.5

<P>Thioredoxin reductase 1 (Trr1) is an antioxidant and redox regulator that functions in governing the cellular redox state and survival against oxidative insults in mammals. However, this selenoprotein is also overexpressed in various forms of malignant cancers, leading to the hypothesis that Trr1 may be a potential target for cancer therapy. A quinone anti-cancer drug, mitomycin C (MMC), has been clinically used in the treatment of several types of tumors, including those of the colon. MMC exerts its activity via ROS induction and further results in DNA cross-linkage. To evaluate the significant role of Trr1 in MMC resistance in human colon cancer (RKO) cells, specific reduction in the expression of Trr1 was achieved using short-hairpin RNA (shRNA)-based interference. Our results showed that stable Trr1 shRNA knockdown manifested higher cellular susceptibility to MMC in comparison to that in wild-type cells. In addition, increased intracellular ROS accumulation appeared in the Trr1 shRNA knockdown cells compared to the RKO wild-type cells, in proportion to a relatively higher fraction of the DNA damage reporter protein phosphorylated histone '관-H2AX'. Notably, a neutral comet assay demonstrated that DNA double-strand breaks were highly induced in the Trr1-deficient cancer cells in the presence of MMC, presumably stimulating cancer cell death. Our results also revealed that MMC-induced apoptosis was associated with enhancement of oxidative damage to DNA. These results suggest that the specific knockdown of Trr1 expression via shRNA vector interference technology may be a potent molecular strategy by which to enhance the effectiveness of MMC-mediated killing in human colon cancer cells, through acceleration of double-strand DNA damage-oxidative stress as a trigger for apoptosis. This implies that Trr1 may be a prime target for enhancing the effectiveness of MMC chemotherapy in combination with specific RNA interference.</P>

Intrinsic toxicity of stable nanosized titanium dioxide using polyacrylate in human keratinocytes

Preeyaporn Koedrith,Yeo Jin Kim,Younghun Kim,강주현,Young Rok Seo 대한독성 유전단백체 학회 2018 Molecular & cellular toxicology Vol.14 No.3

Backgrounds: Trends in the use of an anticoagulant as a dispersing stabilizer are addressed. An effective approach to preparing stable nanosized titanium dioxide (nTiO2) for accurate and systematic assessment of nano- toxicity has not been established. Methods: Among the dispersants tested here, it was found that sodium polyacrylate (PAA) was the most effective dispersant for nTiO2 in culture media. Our study was the first to demonstrate that a stable PAA-dispersed nTiO2 (nTiO2/PAA) suspension showed more toxic than nTiO2 without PAA in human HaCaT keratinocytes. Results: Initially, MTT results showed that the stable nTiO2/PAA dispersion exhibited significantly greater cytotoxicity than nTiO2 without PAA. In addition, the stable nTiO2/PAA dispersion induced markedly more oxidative stress than nTiO2 without PAA. Importantly, the stable nTiO2/PAA dispersion caused DNA breakage to a greater extent than nTiO2 without PAA. Conclusion: Our findings indicated that the anti-coagulant PAA is suitable for preparing homologous dispersed nTiO2 under realistic physiological culture test conditions.

Induction of doxorubicin-mediated apoptosis via thioredoxin reductase 1 RNAi in human colon cancer cells

Preeyaporn Koedrith,Young Rok Seo 대한독성 유전단백체 학회 2011 Molecular & cellular toxicology Vol.7 No.2

In mammals, thioredoxin reductase 1 (Trr1)is of potential importance in defense against oxidative stress and regulation of redox homeostasis. Nevertheless,overexpression of this selenoprotein Trr1 is also manifested in several types of malignant cancers, leading to hypothesis that Trr1 might be a molecular candidate for anticancer drug treatment. An anthracycline antibiotic, doxorubicin (DOX), has been extensively applied in the chemotherapy of solid tumor tissues including colon. Cytotoxification of DOX is targeting on damage to DNA molecules via possible generation of reactive oxygen species (ROS) with consequent inhibition of macromolecule biosynthesis. At present work focusing on specific Trr1 knockdown using short hairpin RNA (shRNA) based viral vector, the important role of Trr1 on DOX resistance in human colon cancer RKO cell was deliberately investigated. Intriguingly,our finding presented that the stable Trr1shRNA knockdown had higher sensitivity to DOX relative to the wild type. With respect to this point,accumulated intracellular ROS was notably stimulated in the Trr1 shRNA defect rather than the wild type. Apparently, it was also direct linkage between ROS level and extent of phosphorylated histone “gamma-H2AX”, indicative of DNA damage. Strikingly, our important observation revealed that in presence of DOX Trr1 deficiency probably accelerated double strand breaks to DNA, provided evidence as neutral comet assay. Additionally, our data demonstrated that DOX-induced apoptosis was also correlated with increment of oxygen radicals damage to DNA. Taken together,it was worthy to conclude that specific reduction of Trr1 expression via shRNA based interference might be a considerable molecular approach to improve effectiveness of DOX-mediated killing in treatment of human colon cancer cells, through stimulation of oxidative insult. This implied that Trr1 might be a plausible target in cancer therapy.

Nanoparticles: Weighing the Pros and Cons from an Eco-genotoxicological Perspective

Preeyaporn Koedrith,Md. Mujibur Rahman,Yu Jin Jang,Dong Yeop Shin,서영록 대한암예방학회 2021 Journal of cancer prevention Vol.26 No.2

The exponential growth of nanotechnology and the industrial production have raised concerns over its impact on human and environmental health and safety (EHS). Although there has been substantial progress in the assessment of pristine nanoparticle toxicities, their EHS impacts require greater clarification. In this review, we discuss studies that have assessed nanoparticle eco-genotoxicity in different test systems and their fate in the environment as well as the considerable confounding factors that may complicate the results. We highlight key mechanisms of nanoparticle-mediated genotoxicity. Then we discuss the reliability of endpoint assays, such as the comet assay, the most favored assessment technique because of its versatility to measure low levels of DNA strand breakage, and the micronucleus assay, which is complementary to the former because of its greater ability to detect chromosomal DNA fragmentation. We also address the current recommendations on experimental design, including environmentally relevant concentrations and suitable exposure duration to avoid false-positive or -negative results. The genotoxicity of nanoparticles depends on their physicochemical features and the presence of co-pollutants. Thus, the effect of environmental processes (e.g., aggregation and agglomeration, adsorption, and transformation of nanoparticles) would account for when determining the actual genotoxicity relevant to environmental systems, and assay procedures must be standardized. Indeed, the engineered nanoparticles offer potential applications in different fields including biomedicine, environment, agriculture, and industry. Toxicological pathways and the potential risk factors related to genotoxic responses in biological organisms and environments need to be clarified before appropriate and sustainable applications of nanoparticles can be established. Key Words DNA damage, Genotoxicology, Nanoparticles, Nanotoxicology, Risk assessment

Integrative toxicogenomics-based approach to risk assessment of heavy metal mixtures/complexes: strategies and challenges

Preeyaporn Koedrith,Hye Lim Kim,Young Rok Seo 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.3

Human exposure to metallic elements ranging from single metal ionic salt, metal compounds, and metal mixtures that may occur naturally, as well as from human activities and industrial applications. Some metals including arsenic, cadmium, chromium, lead, mercury, and nickel in both single element and mixture forms render confounding health effects and ultimately cause cancer. Studies of heavy metal-mediated global aberration using non-targeted multiple toxicogenomic technologies might help to elucidate environmentally relevant disorders, as well as to monitor biomarker of exposure and predict the health risk toward environmental toxicants. We describe recent toxicogenomic studies on heavy metal mixtures as well as relevant mechanism of toxicity and molecular signatures. On the basis of system toxicology approach, integrative toxicogenomic and bioinformatic tools might represent the biological pathways linked to disorders. We also strongly suggest that the toxicogenomic data can be adopted to risk assessment process. Furthermore, we mention challenges in utility of toxicogenomic studies data to risk assessment process of toxicity of metal mixtures. Overall, we realize that application and interpretation of toxicogenomic data regarding to their strengths and weaknesses would potentiate chemical risk assessment.

Sensitizing effect of silencing Ape1/Ref-1 on doxorubicin-induced apoptosis in human carcinoma cells

Preeyaporn Koedrith,Young Rok Seo 대한독성 유전단백체 학회 2011 Molecular & cellular toxicology Vol.7 No.4

Ape1/Ref-1 is a multifunctional protein with major functions in DNA base excision repair system and redox regulation of several transcription factors. However, overexpression of Ape1/Ref-1 is observed in many types of malignant cancers, leading to point that this protein might be a molecular candidate for anticancer drug treatment. A doxorubicin (DOX)has been widely applied in the chemotherapy of solid tumors including lung. Cytotoxification of DOX is targeting on damage to cellular components, particularly DNA molecules, via generation of reactive oxygen species (ROS). Using specific suppression by short hairpin RNA (shRNA)-based viral vector, an important role of Ape1/Ref-1 on DOX resistance in human lung cancer H1299 cell was investigated in this study. Our data revealed that the stable Ape1/Ref-1 shRNA knockdown had higher susceptibility to DOX compared to the wild type. In accordance, intracellular ROS level was notably accelerated in the Ape1/Ref-1 shRNA defect rather than the wild type. Strikingly, our observation represented that in presence of DOX Ape1/Ref-1 deficiency probably stimulated double strand breaks to DNA, detected by neutral comet assay and gamma-H2AX immunoassay, sensitive methods of genotoxicity. Furthermore, our result showed that DOX-induced apoptosis was also correlated with increase in oxygen radicals-generated damage to DNA. We can conclude that Ape1/Ref1-targeted silencing via shRNA-based interference might be a promising molecular strategy to improve effectiveness of DOX-induced apoptosis in treatment of human lung cancer cells, through induction of oxidative insult. This emphasizes that Ape1/Ref-1 might be a prominent therapeutic target in cancer therapy.