Lactic acid in macrophage polarization: A factor in carcinogenesis and a promising target for cancer therapy.

Cancer remains a formidable challenge, continually revealing its intricate nature and demanding novel treatment approaches. Within this intricate landscape, the tumor microenvironment and its dynamic components have gained prominence, particularly macrophages that can adopt diverse polarization states, exerting a profound influence on cancer progression. Recent revelations have spotlighted lactic acid as a pivotal player in this complex interplay. This review systematically explores lactic acid's multifaceted role in macrophage polarization, focusing on its implications in carcinogenesis. We commence by cultivating a comprehensive understanding of the tumor microenvironment and the pivotal roles played by macrophages. The dynamic landscape of macrophage polarization, typified by M1 and M2 phenotypes, is dissected to reveal its substantial impact on tumor progression. Lactic acid, a metabolic byproduct, emerges as a key protagonist, and we meticulously unravel the mechanisms underpinning its generation within cancer cells, shedding light on its intimate association with glycolysis and its transformative effects on the tumor microenvironment. Furthermore, we decipher the intricate molecular framework that underlies lactic acid's pivotal role in facilitating macrophage polarization. Our review underscores lactic acid's dual role in carcinogenesis, orchestrating tumor growth and immune modulation within the tumor microenvironment, thereby profoundly influencing the balance between pro-tumor and anti-tumor immune responses. This duality highlights the therapeutic potential of selectively manipulating lactic acid metabolism for cancer treatment. Exploring strategies to inhibit lactic acid production by tumor cells, novel approaches to impede lactic acid transport in the tumor microenvironment, and the burgeoning field of immunotherapeutic cancer therapies utilizing lactic acid-induced macrophage polarization form the core of our investigation.

Oxali-palladium nanoparticle synthesis, characterization, protein binding, and apoptosis induction in colorectal cancer cells.

This paper focuses on the synthesis of nano-oxali-palladium coated with turmeric extract (PdNPs) using a green chemistry technique based on the reduction in the Pd (II) complex by phytochemicals inherent in turmeric extract. PdNPs were examined and characterized using Field Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS), Fourier Transform Infrared (FTIR), and Atomic Force Microscopy (AFM). Using different spectroscopic and molecular dynamics simulations, a protein-binding analysis of the produced nanoparticle was conducted by observing its interaction with human serum albumin (HSA). Lastly, the cytotoxic effects and apoptotic processes of PdNPs were studied against the HCT116 human colorectal cell line using the MTT assay and flow cytometry tests. According to the findings, PdNPs with spherical and homogenous morphology and a size smaller than 100 nm were generated. In addition, they can induce apoptosis in colorectal cancer cells in a dose-dependent manner with a lower Cc50 (78 µL) than cisplatin and free oxali-palladium against HCT116 cells. The thermodynamic characteristics of protein binding of nanoparticles with HSA demonstrated that PdNPs had a great capacity for quenching and interacting with HSA through hydrophobic forces. In addition, molecular dynamics simulations revealed that free oxali-palladium and PdNP attach to the same area of HSA via non-covalent interactions. It is conceivable to indicate that the synthesized PdNPs are a potential candidate for the construction of novel, nature-based anticancer treatments with fewer side effects and a high level of eco-friendliness.

Acute myeloid leukemias with UBTF tandem duplications are sensitive to menin inhibitors.

ABSTRACT: UBTF tandem duplications (UBTF-TDs) have recently emerged as a recurrent alteration in pediatric and adult acute myeloid leukemia (AML). UBTF-TD leukemias are characterized by a poor response to conventional chemotherapy and a transcriptional signature that mirrors NUP98-rearranged and NPM1-mutant AMLs, including HOX-gene dysregulation. However, the mechanism by which UBTF-TD drives leukemogenesis remains unknown. In this study, we investigated the genomic occupancy of UBTF-TD in transformed cord blood CD34+ cells and patient-derived xenograft models. We found that UBTF-TD protein maintained genomic occupancy at ribosomal DNA loci while also occupying genomic targets commonly dysregulated in UBTF-TD myeloid malignancies, such as the HOXA/HOXB gene clusters and MEIS1. These data suggest that UBTF-TD is a gain-of-function alteration that results in mislocalization to genomic loci dysregulated in UBTF-TD leukemias. UBTF-TD also co-occupies key genomic loci with KMT2A and menin, which are known to be key partners involved in HOX-dysregulated leukemias. Using a protein degradation system, we showed that stemness, proliferation, and transcriptional signatures are dependent on sustained UBTF-TD localization to chromatin. Finally, we demonstrate that primary cells from UBTF-TD leukemias are sensitive to the menin inhibitor SNDX-5613, resulting in markedly reduced in vitro and in vivo tumor growth, myeloid differentiation, and abrogation of the UBTF-TD leukemic expression signature. These findings provide a viable therapeutic strategy for patients with this high-risk AML subtype.

Design, characterization and green synthesis of samarium-decorated magnetic Fe3O4 nanoparticles: cytotoxicity and DNA binding studies.

In this study, we have successfully synthesized magnetic Fe3O4 nanoparticles adorned with samarium (Sm-MNPs) utilizing ginger extract for the very first time. Furthermore, a comprehensive characterization of the nanoparticles along with an exploration of their physicochemical attributes was conducted. The biological functionalities of the synthesized nanoparticles were investigated through a thorough examination of their interaction with calf thymus DNA (ctDNA) using diverse spectroscopic techniques encompassing ultraviolet-visible (UV-Vis) and fluorescence spectroscopy at varying temperatures. Subsequently, we evaluated the cytotoxicity of the magnetic nanoparticles using a colorectal cancer cell model (HCT116 cells) and a tetrazolium colorimetric assay (MTT assay). The characterization of the ginger extract-coated magnetic nanoparticles (ginger-Sm-MNPs) revealed their superparamagnetic nature, nanocrystalline structure, spherical morphology, hydrodynamic size of 155 nm, and uniform distribution. The outcomes from UV-Vis and fluorescence spectroscopy affirmed the binding of ginger-Sm-MNPs with ctDNA. Additionally, the MTT assay demonstrated that the cytotoxicity of ginger-Sm-MNPs surpassed that of both magnetite nanoparticles and ginger extract. Notably, the inhibitory concentrations (IC50) for the green-synthesized nanoparticles after 24 and 48 h of incubation were determined as 198.1 and 135.8 µg/mL, respectively. In conclusion, our study findings suggest the potential utility of ginger-Sm-MNPs as a promising candidate for various biomedical applications.Communicated by Ramaswamy H. Sarma.

The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98-rearranged AML.

Chromosomal translocations involving the NUP98 locus are among the most prevalent rearrangements in pediatric acute myeloid leukemia (AML). AML with NUP98 fusions is characterized by high expression of HOXA and MEIS1 genes and is associated with poor clinical outcome. NUP98 fusion proteins are recruited to their target genes by the mixed lineage leukemia (MLL) complex, which involves a direct interaction between MLL and Menin. Here, we show that therapeutic targeting of the Menin-MLL interaction inhibits the propagation of NUP98-rearrranged AML both ex vivo and in vivo. Treatment of primary AML cells with the Menin inhibitor revumenib (SNDX-5613) impairs proliferation and clonogenicity ex vivo in long-term coculture and drives myeloid differentiation. These phenotypic effects are associated with global gene expression changes in primary AML samples that involve the downregulation of many critical NUP98 fusion protein-target genes, such as MEIS1 and CDK6. In addition, Menin inhibition reduces the expression of both wild-type FLT3 and mutated FLT3-ITD, and in combination with FLT3 inhibitor, suppresses patient-derived NUP98-r AML cells in a synergistic manner. Revumenib treatment blocks leukemic engraftment and prevents leukemia-associated death of immunodeficient mice transplanted with NUP98::NSD1 FLT3-ITD-positive patient-derived AML cells. These results demonstrate that NUP98-rearranged AMLs are highly susceptible to inhibition of the MLL-Menin interaction and suggest the inclusion of AML patients harboring NUP98 fusions into the clinical evaluation of Menin inhibitors.

Exosomes as Rheumatoid Arthritis Diagnostic Biomarkers and Therapeutic Agents.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40-100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell-cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties, and promising results have been observed in this area. By understanding the diversity of exosomal contents and their corresponding targets, it may be possible to diagnose autoimmune diseases. Exosomes can be employed as diagnostic biomarkers for immunological disorders. We here discuss the most recent findings regarding the diagnostic, prognostic, and therapeutic potential of these nanoparticles in rheumatoid arthritis and provide an overview of the evidence pertaining to the biology of exosomes in RA.

Nanoparticle-mediated targeting of the fusion gene RUNX1/ETO in t(8;21)-positive acute myeloid leukaemia.

A hallmark of acute myeloid leukaemias (AMLs) are chromosomal rearrangements that give rise to novel leukaemia-specific fusion genes. Most of these fusion genes are both initiating and driving events in AML and therefore constitute ideal therapeutic targets but are challenging to target by conventional drug development. siRNAs are frequently used for the specific suppression of fusion gene expression but require special formulations for efficient in vivo delivery. Here we describe the use of siRNA-loaded lipid nanoparticles for the specific therapeutic targeting of the leukaemic fusion gene RUNX1/ETO. Transient knockdown of RUNX1/ETO reduces its binding to its target genes and alters the binding of RUNX1 and its co-factor CBFß. Transcriptomic changes in vivo were associated with substantially increased median survival of a t(8;21)-AML mouse model. Importantly, transient knockdown in vivo causes long-lasting inhibition of leukaemic proliferation and clonogenicity, induction of myeloid differentiation and a markedly impaired re-engraftment potential in vivo. These data strongly suggest that temporary inhibition of RUNX1/ETO results in long-term restriction of leukaemic self-renewal. Our results provide proof for the feasibility of targeting RUNX1/ETO in a pre-clinical setting and support the further development of siRNA-LNPs for the treatment of fusion gene-driven malignancies.

Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression.

Despite advances in the clinical management of childhood acute myeloid leukemia (AML) during the last decades, outcome remains fatal in approximately one third of patients. Primary chemoresistance, relapse and acute and long-term toxicities to conventional myelosuppressive therapies still constitute significant challenges and emphasize the unmet need for effective targeted therapies. Years of scientific efforts have translated into extensive insights on the heterogeneous spectrum of genetics and oncogenic signaling pathways of AML and identified a subset of patients characterized by upregulation of HOXA and HOXB homeobox genes and myeloid ecotropic virus insertion site 1 (MEIS1). Aberrant HOXA/MEIS1 expression is associated with genotypes such as rearrangements in Histone-lysine N-methyltransferase 2A (KMT2A-r), nucleoporin 98 (NUP98-r) and mutated nucleophosmin (NPM1c) that are found in approximately one third of children with AML. AML with upregulated HOXA/MEIS1 shares a number of molecular vulnerabilities amenable to recently developed molecules targeting the assembly of protein complexes or transcriptional regulators. The interaction between the nuclear scaffold protein menin and KMT2A has gained particular interest and constitutes a molecular dependency for maintenance of the HOXA/MEIS1 transcription program. Menin inhibitors disrupt the menin-KMT2A complex in preclinical models of KMT2A-r, NUP98-r and NPM1c acute leukemias and its occupancy at target genes leading to leukemic cell differentiation and apoptosis. Early-phase clinical trials are either ongoing or in development and preliminary data suggests tolerable toxicities and encouraging efficacy of menin inhibitors in adults with relapsed or refractory KMT2A-r and NPM1c AML. The Pediatric Acute Leukemia/European Pediatric Acute Leukemia (PedAL/EUPAL) project is focused to advance and coordinate informative clinical trials with new agents and constitute an ideal framework for testing of menin inhibitors in pediatric study populations. Menin inhibitors in combination with standard chemotherapy or other targeting agents may enhance anti-leukemic effects and constitute rational treatment strategies for select genotypes of childhood AML, and provide enhanced safety to avoid differentiation syndrome. In this review, we discuss the pathophysiological mechanisms in KMT2A-r, NUP98-r and NPM1c AML, emerging molecules targeting the HOXA/MEIS1 transcription program with menin inhibitors as the most prominent examples and future therapeutic implications of these agents in childhood AML.

Synergistic cellulose-based nanocomposite packaging and cold plasma decontamination for extended saffron preservation.

Sterilization of saffron packaging and maintaining the quality of saffron content are the main priorities in saffron preservation. Common modalities do not offer lasting saffron preservation and it is urgent to develop novel packaging approaches from renewable resources and prevent packaging waste. Here, simultaneous decontamination and quality maintenance of saffron is demonstrated, for the first time, through the synergistic application of nano-clay-loaded carboxymethyl cellulose (CMC)/polyvinyl alcohol (PVA) nanocomposites (CNCs) and cold plasmas (CP). Compared to the separate uses of CP and CMC/PVA/nano clay, our results confirm the synergies between CP and CMC/PVA/nano clay cause complete inactivation of Escherichia coli bacteria, while not significantly affecting the concentrations of the essential saffron components (safranal, crocin, and picrocrocin). Overall, the CP-treated CMC/PVA/nano clay fosters saffron preservation, through contamination removal and quality maintenance of the food product. The synergistic application of CP and CMC/PVA/nano clay thus represents a promising strategy for packaging, sterilization, and preservation of high-value food products.

Detection of urban trees sensitivity to air pollution using physiological and biochemical leaf traits in Tehran, Iran.

The increased population in megacities has recently exacerbated the need to combat air pollution. This study examined the concept that the sensitivity and tolerance of urban plant species to air pollution might be used to determine Tehran, Iran's air quality and obtain suitable urban greening. The air pollution tolerance index (APTI) was derived using the total chlorophyll, relative water content, pH, and ascorbic acid content of leaf extract from Morus alba, Ailanthus altissima, and Salix babylonica trees as an indicator of the sensitivity and tolerance of urban plant species. A. altissima and S. babylonica, with APTI values of 11.15 and 11.08, respectively, were sensitive to air pollution and can be employed as bioindicators, whereas M. alba, with an APTI value of 14.08, exhibited moderate resistance to air pollution and is therefore recommended for urban planting. Furthermore, the content of enzymatic and non-enzymatic parameters (carotenoid, phenol, and flavonoids) and proline concentration in the polluted seasons and sites (3 and 4) have been increased in M. alba. Collectively, we expect our findings to contribute to the rapidly growing body of research aiming to find a suitable urban greening for a wide range of polluted megacities.

Optical and structural properties of Sn and Ag-doped PbS/PVA nanocomposites synthesized by chemical bath deposition.

In this work, Sn and Ag doped PbS/PVA nanocomposites, in three different concentrations were successfully prepared using the low-cost and simple method of chemical bath deposition (CBD). X-ray diffraction patterns confirmed the formation of the PbS cubic phase in all of the nanocomposites. FE-SEM images showed that PbS NPs are cubic in shape and the doping can alter the shape of grains. DLS analysis applied for solution NPs exhibited a 175 nm size distribution for PbS NPs and decreased by doping Ag and Sn to almost 100 nm and 110 nm, respectively. Optical absorption spectra showed the blue phenomena and the band gaps of Sn: PbS/PVA and Ag: PbS/PVA nanocomposites increased with adding Sn and Ag from 3.08 eV for pure PVA/PbS to 3.33 eV for Sn doped and 3.43 eV for Ag-doped samples. The nonlinear refractive index is decreased from 0.55 m2 W-1 for pure PVA/PbS to 0.11 m2 W-1 and 0.13 m2 W-1 for Sn and Ag-doped samples, respectively. Hence, doping Ag and Sn enhanced the optical sensitivity issue of nanocomposites and raised the optical resistivity. Collectively, our results can be useful in the design of linear and nonlinear optical devices such as sensors and optical switches and limiters.

Arc and pulsed spark discharge inactivation of pathogenic P. aeruginosa, S. aureus, M. canis, T. mentagrophytes, and C. albicans microorganisms.

There is a strong and ever-escalating need for sterilization tools that are effective against a broad range of pathogenic microorganisms. To address this issue, this study evaluates the inactivation potential of arc and pulsed spark plasma discharges on Pseudomonas aeruginosa, Staphylococcus aureus, Microsporum canis, Trichophyton mentagrophytes, and Candida albicans microorganisms. Our results show that the electrical discharge plasma systems are effective in the inactivation of pathogenic microorganisms. The inactivation of the considered strains was greatly affected by the type of microorganisms. Higher viability losses of the pathogenic strains were observed in bacterial strains than in the fungal strains. Moreover, in the case of fungal strains, the population of C. albicans was decreased the most, followed by Trichophyton mentagrophyte, while the population of Microsporum canis was decreased the least. Besides, the arc discharge system was compared with the pulsed spark discharge system. It can be obtained from the results that the pulsed spark discharge treatment successfully enhanced the reduction of the pathogenic cells more than the arc discharge treatment. The higher efficiency of the pulsed spark discharge is due to the generation of discharge streamers on the water surface. The SEM analyses showed that electrical discharge plasmas produced serious damage to pathogenic eukaryotic and prokaryotic microorganisms. Also, the plasma-induced changes in pH values and temperature values were measured. The pulsed spark discharge-treated samples have more significant changes in pH value while arc discharge-treated samples have larger temperature changes.

SMARCA5 interacts with NUP98-NSD1 oncofusion protein and sustains hematopoietic cells transformation.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by accumulation of aberrantly differentiated hematopoietic myeloid progenitor cells. The karyotyping-silent NUP98-NSD1 fusion is a molecular hallmark of pediatric AML and is associated with the activating FLT3-ITD mutation in > 70% of the cases. NUP98-NSD1 fusion protein promotes myeloid progenitor self-renewal in mice via unknown molecular mechanism requiring both the NUP98 and the NSD1 moieties. METHODS: We used affinity purification coupled to label-free mass spectrometry (AP-MS) to examine the effect of NUP98-NSD1 structural domain deletions on nuclear interactome binding. We determined their functional relevance in NUP98-NSD1 immortalized primary murine hematopoietic stem and progenitor cells (HSPC) by inducible knockdown, pharmacological targeting, methylcellulose assay, RT-qPCR analysis and/or proximity ligation assays (PLA). Fluorescence recovery after photobleaching and b-isoxazole assay were performed to examine the phase transition capacity of NUP98-NSD1 in vitro and in vivo. RESULTS: We show that NUP98-NSD1 core interactome binding is largely dependent on the NUP98 phenylalanine-glycine (FG) repeat domains which mediate formation of liquid-like phase-separated NUP98-NSD1 nuclear condensates. We identified condensate constituents including imitation switch (ISWI) family member SMARCA5 and BPTF (bromodomain PHD finger transcription factor), both members of the nucleosome remodeling factor complex (NURF). We validated the interaction with SMARCA5 in NUP98-NSD1+ patient cells and demonstrated its functional role in NUP98-NSD1/FLT3-ITD immortalized primary murine hematopoietic cells by genetic and pharmacological targeting. Notably, SMARCA5 inhibition did not affect NUP98-NSD1 condensates suggesting that functional activity rather than condensate formation per se is crucial to maintain the transformed phenotype. CONCLUSIONS: NUP98-NSD1 interacts and colocalizes on the genome with SMARCA5 which is an essential mediator of the NUP98-NSD1 transformation in hematopoietic cells. Formation of NUP98-NSD1 phase-separated nuclear condensates is not sufficient for the maintenance of transformed phenotype, which suggests that selective targeting of condensate constituents might represent a new therapeutic strategy for NUP98-NSD1 driven AML.

The current and advanced therapeutic modalities for wound healing management.

Ever-increasing demands on improving efficiencies of wound healing procedures are a strong driving force for the development of replacement approaches. This review focuses on wound healing management from the point of formation to the point of healing procedures. The most important usual healing modality with key characteristic is explained and their limitations are discussed. Novel interesting approaches are presented with a concentration of the unique features and action mechanisms. Special attention is paid to gas plasma and nanotechnology impact on wound healing management from fundamental processes to beneficial outcomes. Challenges and opportunities for the future trend that combined common protocols and emerging technologies are discussed.

Combining Nanotechnology and Gas Plasma as an Emerging Platform for Cancer Therapy: Mechanism and Therapeutic Implication.

Nanomedicine and plasma medicine are innovative and multidisciplinary research fields aiming to employ nanotechnology and gas plasma to improve health-related treatments. Especially cancer treatment has been in the focus of both approaches because clinical response rates with traditional methods that remain improvable for many types of tumor entities. Here, we discuss the recent progress of nanotechnology and gas plasma independently as well as in the concomitant modality of nanoplasma as multimodal platforms with unique capabilities for addressing various therapeutic issues in oncological research. The main features, delivery vehicles, and nexus between reactivity and therapeutic outcomes of nanoparticles and the processes, efficacy, and mechanisms of gas plasma are examined. Especially that the unique feature of gas plasma technology, the local and temporally controlled deposition of a plethora of reactive oxygen, and nitrogen species released simultaneously might be a suitable additive treatment to the use of systemic nanotechnology therapy approaches. Finally, we focus on the convergence of plasma and nanotechnology to provide a suitable strategy that may lead to the required therapeutic outcomes.

Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers.

Gastric and esophageal cancers are as main cancers of the gastrointestinal (GI) tract, which are associated with poor diagnosis and survival. Several efforts were made in the past few decades to finding effective therapeutic approaches, but these approaches had several problems. Finding new biomarkers is a critical step in finding new approaches for the treatment of these cancers. Finding new biomarkers that cover various aspects of the diseases could provide a choice of suitable therapies and better monitoring of patients with these cancers. Among several biomarkers tissue specific and circulating microRNAs (miRNAs) have emerged as powerful candidates in the diagnosis of gastric and esophageal cancers. MiRNAs are small noncoding single-stranded RNA molecules that are found in the blood and regulate gene expression. These have numerous characteristics that make them suitable for being used as ideal biomarkers in cancer diagnosis. Research has indicated that the level and profile of miRNA in serum and plasma are very high. They are potentially noninvasive and sensitive enough to detect tumors in their primary stages of infection. Multiple lines of evidence indicate that the presence, absence, or deregulation of several circulating miRNAs (i.e., let-7a, miR-21, miR-93, miR-192a, miR-18a, and miR-10b for gastric cancer, and miR-21, miR-375, miR-25-3p, miR-151a-3p, and miR-100-3p for esophageal cancer) are associated with initiation and progression of gastric and esophageal cancers. The aim of this review is to highlight the recent advances in the roles of miRNAs in diagnosis and treatment of gastric and esophageal cancers.

Carcinogenic and non-carcinogenic health risks of metal(oid)s in tap water from Ilam city, Iran.

One of the most important pathways for exposure to metals is drinking water ingestion. Chronic or acute exposure to metals can endanger the health of the exposed population, and hence, estimation of human health risks is crucial. In the current study for the first time, the concentrations of Mercury (Hg), Arsenic (As), Zinc (Zn), Lead (Pb) and Cobalt (Co) in 120 collected tap water samples (2015, July-November) from Ilam city, Iran were investigated using flame atomic absorption spectrophotometer. Also, the metal-induced carcinogenic and non-carcinogenic risks for consumers exposed to tap drinking water were calculated. The average (range) concentrations of Hg, Zn, As, Pb and Co were defined as 0.40 ± 0.10 µg/L (ND-0.9 µg/L), 5014 ± 5707 µg/L (2900.00-5668.33 µg/L), 21.008 ± 2.876 µg/L (3.5-62 µg/L), 30.38 ± 5.56 µg/L (6-87 µg/L), and 11.34 ± 1.61 µg/L (0.1-50 µg/L), respectively. Average concentrations of all examined metals were significantly higher than WHO and national standard recommended limits. The ranking order of metals concentrations in the tap drinking water was Zn > Pb > As > Co > Hg. Except for Hg and Co, at least one age group consumers were at considerable non-carcinogenic risks induced by Zn, As and Pb [Target Hazard Quotient (THQ > 1)]. The rank order of age groups consumers based on THQ and Incremental lifetime cancer risk (ILCR) was <1 years >1-9 years > 20 + years > 10-19 years. The calculated ILCR for As in all age groups were higher than 10-3 value. All age groups of consumers in Ilam city, especially infants (<1 years) and children (1-10 years), are at considerable non-carcinogenic and carcinogenesis risk.