RET Alterations Differentiate Molecular Profile of Medullary Thyroid Cancer.

PURPOSE: Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are predominantly reported in RET oncogene, and lower-frequency alterations are reported in KRAS and BRAF. Nevertheless, there is an unmet need existing to analyze the MTC in the Indian cohort by using in-depth sequencing techniques that go beyond the identification of known therapeutic biomarkers. MATERIALS AND METHODS: Here, we characterize MTC using integrative whole-exome and whole-transcriptome sequencing of 32 MTC tissue samples. We performed clinically relevant variant analysis, molecular pathway analysis, tumor immune-microenvironment analysis, and structural characterization of RET novel mutation. RESULTS: Mutational landscape analysis shows expected RET mutations in 50% of the cases. Furthermore, we observed mutations in known cancer genes like KRAS, HRAS, SF3B1, and BRAF to be altered only in the RET-negative cohort. Pathway analysis showed differential enrichment of mutations in transcriptional deregulation genes in the RET-negative cohort. Furthermore, we observed novel RET kinase domain mutation Y900S showing affinity to RET inhibitors accessed via molecular docking and molecular dynamics simulation. CONCLUSION: Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.

Singleton mutations in large-scale cancer genome studies: uncovering the tail of cancer genome.

Singleton or low-frequency driver mutations are challenging to identify. We present a domain driver mutation estimator (DOME) to identify rare candidate driver mutations. DOME analyzes positions analogous to known statistical hotspots and resistant mutations in combination with their functional and biochemical residue context as determined by protein structures and somatic mutation propensity within conserved PFAM domains, integrating the CADD scoring scheme. Benchmarked against seven other tools, DOME exhibited superior or comparable accuracy compared to all evaluated tools in the prediction of functional cancer drivers, with the exception of one tool. DOME identified a unique set of 32 917 high-confidence predicted driver mutations from the analysis of whole proteome missense variants within domain boundaries across 1331 genes, including 1192 noncancer gene census genes, emphasizing its unique place in cancer genome analysis. Additionally, analysis of 8799 TCGA (The Cancer Genome Atlas) and in-house tumor samples revealed 847 potential driver mutations, with mutations in tyrosine kinase members forming the dominant burden, underscoring its higher significance in cancer. Overall, DOME complements current approaches for identifying novel, low-frequency drivers and resistant mutations in personalized therapy.

Mitocurcumin utilizes oxidative stress to upregulate JNK/p38 signaling and overcomes Cytarabine resistance in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a type of blood cancer that is characterized by the rapid growth of abnormal myeloid cells. The goal of AML treatment is to eliminate the leukemic blasts, which is accomplished through intensive chemotherapy. Cytarabine is a key component of the standard induction chemotherapy regimen for AML. However, despite a high remission rate, 70-80% of AML patients relapse and develop resistance to Cytarabine, leading to poor clinical outcomes. Mitocurcumin (MitoC), a derivative of curcumin that enters mitochondria, leading to a drop in mitochondrial membrane potential and mitophagy induction. Further, it activates oxidative stress-mediated JNK/p38 signaling to induce apoptosis. MitoC demonstrated a preferential ability to kill leukemic cells from AML cell lines and patient-derived leukemic blasts. RNA sequencing data suggests perturbation of DNA damage response and cell proliferation pathways in MitoC-treated AML. Elevated reactive oxygen species (ROS) in MitoC-treated AML cells resulted in significant DNA damage and cell cycle arrest. Further, MitoC treatment resulted in ROS-mediated enhanced levels of p21, which leads to suppression of CHK1, RAD51, Cyclin-D and c-Myc oncoproteins, potentially contributing to Cytarabine resistance. Combinatorial treatment of MitoC and Cytarabine has shown synergism, increased apoptosis, and enhanced DNA damage. Using AML xenografts, a significant reduction of hCD45+ cells was observed in AML mice bone marrow treated with MitoC (mean 0.6%; range0.04%-3.56%) compared to control (mean 38.2%; range10.1%-78%), p = 0.03. The data suggest that MitoC exploits stress-induced leukemic oxidative environment to up-regulate JNK/p38 signaling to lead to apoptosis and can potentially overcome Cytarabine resistance via ROS/p21/CHK1 axis.

Whole exome sequencing uncovers HRAS mutations as potential mediators of resistance to metronomic chemotherapy.

OBJECTIVES: The aim of this pilot study is to identify the genetic factors that contribute to the response of metronomic chemotherapy in head and neck squamous cell carcinoma (HNSCC) patients using whole-exome sequencing (WES). This study would facilitate the identification of predictive biomarkers, which would enable personalized treatment strategies and improve treatment outcomes for patients with HNSCC. MATERIALS AND METHODS: We have selected patients with recurrent head and neck cancer who underwent metronomic chemotherapy. Sequential tumor biopsies were collected from the patients at different stages of treatment to capture the genomic alterations and tumor evolution during metronomic chemotherapy and sequenced using WES. RESULTS: We identified several known HNSCC hallmark genes reported in COSMIC, including KMT2B, NOTCH1, FAT1, TP53, HRAS, CASP8, and CDKN2A. Copy number alteration analysis revealed amplifications and deletions in several oncogenic and tumor suppressor genes. COSMIC Mutational Signature 15 associated with defective DNA mismatch repair was enriched in 73% of HNSCC samples. Further, the comparison of genomic alterations between responders and non-responders identified HRAS gene uniquely mutated in non-responders that could potentially contribute to resistance against metronomic chemotherapy. DISCUSSION: Our findings corroborate the molecular heterogeneity of recurrent HNSCC tumors and establish an association between HRAS mutations and resistance to metronomic chemotherapy, suggesting HRAS as a potential therapeutic target. Combining HRAS inhibitors with metronomic regimens could improve treatment sensitivity in HRAS-mutated HNSCC patients. Further studies are needed to fully elucidate the genomic mechanisms underlying the response to metronomic chemotherapy.

Association of Cutibacterium acnes with human thyroid cancer.

Introduction: The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer. Methods: We sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer. Results: Our analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer. Conclusion: Cutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better.

Gastrointestinal Lesions and Its Associated Factors in Adult Males With Iron Deficiency Anaemia: A Cross-Sectional Study From Tertiary Care Centre of North India.

Background Around 30% of the world's population suffers from iron deficiency anaemia (IDA). The standard evaluation for IDA involves upper and lower endoscopy, which allows for the confirmation of pathology of the gastrointestinal tract (GIT) induced due to IDA through iron malabsorption mechanism or loss of blood. Assessing the prevalence of lesions of GIT of significant nature among males having IDA, was the goal of our study. Methods Our cross-sectional study was conducted for two years and involved 152 males (adults) with confirmed cases of IDA from the Outpatient (OPD) and In-patient (IPD) in the present hospital. Following collecting consent (both informed and written in nature), patient-specific data was collected in a standardized form, and a blood sample was taken for laboratory testing. The analyses were done at a 5% level of significance; an association was considered significant if the p-value < 0.05. Results The average age of the study participants was 59.6 years. The commonest lesions reported were antral gastritis (9.9%) and H. pylori gastritis (7.2%) in upper GI; and haemorrhoid (9.2%) and anal fissure (3.9%) in lower GI. The overall prevalence of any GI lesions was 65.1%. The GI lesions were significantly associated higher among men with age > 50 years (73.7%). The presence of occult blood in stools (p < 0.0001) and parasites in stools (p=0.0001) were significantly related to the presence of GI lesions. Conclusion GI lesions are frequently detected in males with IDA. Whether it is symptomatic male or asymptomatic male with anaemia refractory to iron treatment, GIT should be evaluated in them.

Osimertinib for lung cancer cells harboring low-frequency EGFR T790M mutation.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, shows significant benefit among patients with EGFR T790M mutation at disease progression. We analyzed the whole exome sequence of 48 samples obtained from 16 lung cancer patients with a longitudinal follow-up: treatment-naïve-baseline primary tumors positive for EGFR activating-mutations, paired re-biopsies upon disease progression but negative for EGFR T790M mutation based on qPCR, and their matched normal blood samples. Our Next generation sequencing (NGS) analysis identified an additional set of 25% re-biopsy samples to harbor EGFR T790M mutation occurring at a low-allele frequency of 5% or less, undetectable by conventional qPCR-based assays. Notably, the clinical utility of osimertinib among patients harboring low-allele frequency of EGFR T790M in tissue biopsy upon disease progression remains less explored. We established erlotinib-resistant PC-9R cells and twenty single-cell sub-clones from erlotinib-sensitive lung cancer PC-9 cells using in vitro drug-escalation protocol. NGS and allele-specific PCR confirmed the low-allele frequency of EGFR T790M present at 5% with a 100-fold higher resistance to erlotinib in the PC-9R cells and its sub-clones. Additionally, luciferase tagged PC-9, and PC-9R cells were orthotopically injected through the intercostal muscle into NOD-SCID mice. The orthotopic lung tumors formed were observed by non-invasive bioluminescence imaging. Consistent with in vitro data, osimertinib, but not erlotinib, caused tumor regression in mice injected with PC-9R cells, while both osimertinib and erlotinib inhibited tumors in mice injected with PC-9 cells. Taken together, our findings could extend the benefit of osimertinib treatment to patients with low EGFR T790M mutation allele frequency on disease progression.

TMC-SNPdb 2.0: an ethnic-specific database of Indian germline variants.

Cancer is a somatic disease. The lack of Indian-specific reference germline variation resources limits the ability to identify true cancer-associated somatic variants among Indian cancer patients. We integrate two recent studies, the GenomeAsia 100K and the Genomics for Public Health in India (IndiGen) program, describing genome sequence variations across 598 and 1029 healthy individuals of Indian origin, respectively, along with the unique variants generated from our in-house 173 normal germline samples derived from cancer patients to generate the Tata Memorial Centre-SNP database (TMC-SNPdb) 2.0. To show its utility, GATK/Mutect2-based somatic variant calling was performed on 224 in-house tumor samples to demonstrate a reduction in false-positive somatic variants. In addition to the ethnic-specific variants from GenomeAsia 100K and IndiGenomes databases, 305 132 unique variants generated from 173 in-house normal germline samples derived from cancer patients of Indian origin constitute the Indian specific, TMC-SNPdb 2.0. Of 305 132 unique variants, 11.13% were found in the coding region with missense variants (31.3%) as the most predominant category. Among the non-coding variations, intronic variants (49%) were the highest contributors. The non-synonymous to synonymous SNP ratio was observed to be 1.9, consistent with the previous version of TMC-SNPdb and literature. Using TMC SNPdb 2.0, we analyzed a whole-exome sequence from 224 in-house tumor samples (180 paired and 44 orphans). We show an average depletion of 3.44% variants per paired tumor and significantly higher depletion (P-value < 0.001) for orphan tumors (4.21%), demonstrating the utility of the rare, unique variants found in the ethnic-specific variant datasets in reducing the false-positive somatic mutations. TMC-SNPdb 2.0 is the most exhaustive open-source reference database of germline variants occurring across 1800 Indian individuals to analyze cancer genomes and other genetic disorders. The database and toolkit package is available for download at the following: Database URL  http://www.actrec.gov.in/pi-webpages/AmitDutt/TMCSNPdb2/TMCSNPdb2.html.

Fusobacterium nucleatum is associated with inflammation and poor survival in early-stage HPV-negative tongue cancer.

Persistent pathogen infection is a known cause of malignancy, although with sparse systematic evaluation across tumor types. We present a comprehensive landscape of 1060 infectious pathogens across 239 whole exomes and 1168 transcriptomes of breast, lung, gallbladder, cervical, colorectal, and head and neck tumors. We identify known cancer-associated pathogens consistent with the literature. In addition, we identify a significant prevalence of Fusobacterium in head and neck tumors, comparable to colorectal tumors. The Fusobacterium-high subgroup of head and neck tumors occurs mutually exclusive to human papillomavirus, and is characterized by overexpression of miRNAs associated with inflammation, elevated innate immune cell fraction and nodal metastases. We validate the association of Fusobacterium with the inflammatory markers IL1B, IL6 and IL8, miRNAs hsa-mir-451a, hsa-mir-675 and hsa-mir-486-1, and MMP10 in the tongue tumor samples. A higher burden of Fusobacterium is also associated with poor survival, nodal metastases and extracapsular spread in tongue tumors defining a distinct subgroup of head and neck cancer.

Managing arsenic (V) toxicity by phosphate supplementation in rice seedlings: modulations in AsA-GSH cycle and other antioxidant enzymes.

The toxic and non-essential metalloid arsenic (As) is ubiquitous in the environment with its absorption from the soil into the plants' roots posing detrimental effects on the crop plants and hence the food availability and food security are also threatened. The present study was intended to reduce the As-induced toxicity in rice seedlings (Oryza sativa L.) by phosphate (PO43-). For this, three concentrations of potassium phosphate (KH2PO4), 50, 100 and 150 µM were supplemented along with 50 µM As exposure to hydroponically grown 7-day-old rice seedlings. Supplementation of PO43- significantly recovered arsenic-induced diminutions in growth parameters and photosynthetic pigment contents which were due to the significant increase in superoxide radical (SOR, O2•¯) and hydrogen peroxide (H2O2). Supplementation of 50 µM PO43- could significantly increase the activity of APX (ascorbate peroxidase) and GR (glutathione reductase) while 100 µM PO43- could increase the activity of DHAR (dehydroascorbate reductase) and monodehydroascorbate reductase (MDHAR). As the amount of PO43- was increased, the ratio of AsA/DHA (reduced to oxidized ascorbate) and GSH/GSSG (reduced to oxidized glutathione) was increased significantly due to increase in the reduced form of the non-enzymes i.e. AsA and GSH. The activity of SOD (superoxide dismutase) and GPX (guaiacol peroxidase) decreased significantly after a substantive increase in their activities due to As stress while the CAT (catalase) activity further enhanced after the supplementation of 50 and 100 µM PO43-. Thus, the As-induced oxidative stress in the rice seedlings was managed by concerted modulations in the activities of SOD, GPX, CAT and AsA-GSH cycle enzymes and metabolites.

Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations.

INTRODUCTION: Unlike lung adenocarcinoma patients, there is no FDA-approved targeted-therapy likely to benefit lung squamous cell carcinoma patients. MATERIALS AND METHODS: We performed survival analyses of lung squamous cell carcinoma patients harboring therapeutically relevant alterations identified by whole exome sequencing and mass spectrometry-based validation across 430 lung squamous tumors. RESULTS: We report a mean of 11.6 mutations/Mb with a characteristic smoking signature along with mutations in TP53 (65%), CDKN2A (20%), NFE2L2 (20%), FAT1 (15%), KMT2C (15%), LRP1B (15%), FGFR1 (14%), PTEN (10%) and PREX2 (5%) among lung squamous cell carcinoma patients of Indian descent. In addition, therapeutically relevant EGFR mutations occur in 5.8% patients, significantly higher than as reported among Caucasians. In overall, our data suggests 13.5% lung squamous patients harboring druggable mutations have lower median overall survival, and 19% patients with a mutation in at least one gene, known to be associated with cancer, result in significantly shorter median overall survival compared to those without mutations. CONCLUSIONS: We present the first comprehensive landscape of genetic alterations underlying Indian lung squamous cell carcinoma patients and identify EGFR, PIK3CA, KRAS and FGFR1 as potentially important therapeutic and prognostic target.

Identifying cancer driver genes from functional genomics screens.

With the emerging advances made in genomics and functional genomics approaches, there is a critical and growing unmet need to integrate plural datasets in order to identify driver genes in cancer. An integrative approach, with the convergence of multiple types of genetic evidence, can limit false positives through a posterior filtering strategy and reduce the need for multiple hypothesis testing to identify true cancer vulnerabilities. We performed a pooled shRNA screen against 906 human genes in the oral cancer cell line AW13516 in triplicate. The genes that were depleted in the screen were integrated with copy number alteration and gene expression data and ranked based on ROAST analysis, using an integrative scoring system, DepRanker, to compute a Rank Impact Score (RIS) for each gene. The RIS-based ranking of candidate driver genes was used to identify the putative oncogenes AURKB and TK1 as essential for oral cancer cell proliferation. We validated the findings, showing that shRNA mediated genetic knockdown of TK1 or pharmacological inhibition of AURKB by AZD-1152 HQPA in AW13516 cells could significantly impede their proliferation. Next we analysed alterations in AURKB and TK1 genes in head and neck cancer and their association with prognosis using data on 528 patients obtained from TCGA. Patients harbouring alterations in AURKB and TK1 genes were associated with poor survival. To summarise, we present DepRanker as a simple yet robust package with no third-party dependencies for the identification of potential driver genes from a pooled shRNA functional genomic screen by integrating results from RNAi screens with gene expression and copy number data. Using DepRanker, we identify AURKB and TK1 as potential therapeutic targets in oral cancer. DepRanker is in the public domain and available for download at http://www.actrec.gov.in/pi-webpages/AmitDutt/DepRanker/DepRanker.html.

Optimising Results of Nasal Tip Rotation Applying Combination of Nasolabial Angle and Lip-Columellar Angle in Tandem in Patients Operated by "Cock-up" Alar Cartilage Flaps Technique.

Background Setting the angle of tip rotation is of utmost importance in achieving satisfactory results in rhinoplasty. Conventionally the upward rotation of the tip requires shortening of the septum by caudal resection and shortening of the lateral walls by cephalic trim of the alar cartilages. The results are usually assessed subjectively. We describe the use of objective parameters to ensure accuracy of nasal tip rotation in patients operated with "cock-up" alar cartilage flaps, a modification of the cephalic trim. Methods Fifteen patients with a long nose having adequate width of lateral crura, desiring a shorter nose with upward tip rotation, were included in the study. Values of preoperative and desired nasolabial angle (from morphed images), and the derived columellar-labial angle were documented. Nasal tip rotation was set to the derived angle and maintained using cock-up alar cartilage flaps. The outcome was evaluated by digital measurements of the nasolabial angle and patients' feedback by Rhinoplasty Outcome Evaluation (ROE) score. Results Satisfactory tip rotation and an aesthetic supratip area could be achieved. The difference in preoperative and postoperative nasolabial angles was statistically significant (p value < 0.0001). The difference in desired and the obtained nasolabial angle was not significant (p value 0.085). The results were maintained on subsequent follow-up. Conclusion Application of angles in practice and use of K-wire template helps us achieve accurate and consistent results. Cock-up flap is an effective technique-to obtain an open nasolabial angle and a desirable supratip region by making use of tissues otherwise discarded.

Loss of malin, but not laforin, results in compromised autophagic flux and proteasomal dysfunction in cells exposed to heat shock.

Heat stress to a cell leads to the activation of heat shock response, which is required for the management of misfolded and unfolded proteins. Macroautophagy and proteasome-mediated degradation are the two cellular processes that degrade polyubiquitinated, misfolded proteins. Contrasting pieces of evidence exist on the effect of heat stress on the activation of the above-mentioned degradative pathways. Laforin phosphatase and malin E3 ubiquitin ligase, the two proteins defective in Lafora neurodegenerative disorder, are involved in cellular stress response pathways and are required for the activation of heat shock transcription factor - the heat shock factor 1 (HSF1) - and, consequently, for cellular protection under heat shock. While the role of laforin and malin in the proteolytic pathways is well established, their role in cellular recovery from heat shock was not explored. To address this, we investigated autophagic flux, proteasomal activity, and the level of polyubiquitinated proteins in Neuro2a cells partially silenced for laforin or malin protein and exposed to heat shock. We found that heat shock was able to induce autophagic flux, proteasomal activity and reduce the polyubiquitinated proteins load in the laforin-silenced cells but not in the malin-deficient cells. Loss of malin leads to reduced proteasomal activity in the heat-shocked cells. Taken together, our results suggest a distinct mode of action for laforin and malin in the heat shock-induced proteolytic processes.

Titanium dioxide nanoparticles augment allergic airway inflammation and Socs3 expression via NF-κB pathway in murine model of asthma.

Titanium dioxide nanoparticles (nTiO2) previously considered to possess relatively low toxicity both in vitro and in vivo, although classified as possibly carcinogenic to humans. Also, their adjuvant potential has been reported to promote allergic sensitization and modulate immune responses. Previously, in OVA induced mouse model of asthma we found high expression of Socs3 and low expression of Stat3 and IL-6. However, a clear understanding regarding the signaling pathways associated with nTiO2 adjuvant effect in mouse model of asthma is lacking. In the present study we investigated the status of Stat3/IL-6 and Socs3 and their relationship with NF-κB, with nTiO2 as an adjuvant in mouse model of asthma. nTiO2 when administered with ovalbumin (OVA) during sensitization phase augmented airway hyper-responsiveness (AHR), biochemical markers of lung damage and a mixed Th2/Th1 dependent immune response. At the same time, we observed significant elevation in the levels of Stat3, Socs3, NF-κB, IL-6 and TNF-α. Furthermore, transient in vivo blocking of NF-κB by NF-κB p65 siRNA, downregulated the expression of Socs3, IL-6 and TNF-α. Our study, thus, shows that nTiO2 exacerbate the inflammatory responses in lungs of pre-sensitized allergic individuals and that these changes are regulated via NF-κB pathway.

FoxO3a-mediated autophagy is down-regulated in the laforin deficient mice, an animal model for Lafora progressive myoclonus epilepsy.

Lafora disease (LD) is an autosomal recessive disorder characterized by epileptic seizures, neurodegeneration and accumulation of polyglucosan bodies (Lafora bodies), arising due to defects in either the laforin protein phosphatase or the malin ubiquitin ligase. Among the multiple cellular pathways affected in LD, the specific cause of the autophagy blockade remains unknown. The autophagy impairment however is known to precede the formation of Lafora bodies in the LD mice models. We show here the involvement of a transcription factor, FoxO3a, to be a possible cause for the autophagic defect in cellular and animal models of LD. We find that the expression levels of FoxO3a and its targets Map1LC3b and Atg12 to be at lower levels in laforin-deficient cells and mice. We also find FoxO3a to be regulated indirectly by laforin through the activity of serum/glucocorticoid induced kinase, SGK1. Our results suggest that FoxO3a exerts a negative control over mTOR, and its loss could result in autophagic defects in LD associated with laforin deficiency.

Integrating techniques to re-establish dentogingival esthetics.

The aim of this article was to report the clinical case of a male patient of 20 years with hyperpigmented gingiva and moderate fluorosis, whose smile was reestablished by the use of a laser assisted depigmentation procedure, an enamel microabrasion technique, followed by at-home bleaching and subsequent remineralization therapy. The association of these techniques presented excellent results and the patient was satisfied. All techniques are painless, fast and easy to perform, in addition to preserving the hard and soft dental structure. Treatment showed immediate and permanent results; these techniques must be divulged among professionals and their patients.

Metal accumulation, growth, antioxidants and oil yield of Brassica juncea L. exposed to different metals.

In agricultural fields, heavy metal contamination is responsible for limiting the crop productivity and quality. This study reports that the plants of Brassica juncea L. cv. Pusa bold grown on contaminated substrates [Cu, Cr(VI), As(III), As(V)] under simulated field conditions have shown translocation of metals to the upper part and its sequestration in the leaves without significantly affecting on oil yield, except for Cr and higher concentration of As(V), compared to control. Decrease in the oil content in As(V) treated plants was observed in a dose dependent manner; however, maximum decrease was recorded in Cr treated plants. Among all the metal treatments, Cr was the most toxic as evident from the decrease in oil content, growth parameters and antioxidants. The accumulation of metals was below the detection limit in the seeds grown on 10 and 30 mg kg(-1) As(III) and Cr(VI); 10 mg kg(-1) As(V)) and thus can be recommended only for oil cultivation.