Department of Life Sciences

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Browsing Department of Life Sciences by Subject "Arsenic"

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    Identification of candidate tumor suppressor genes’ loci on chromosome 9 associated with the development of arsenic induced urinary bladder cancer in West Bengal, India
    Ghosh, Amlan
    The etiological link of arsenic with bladder cancer (BC) is well established across the globe. The molecular pathogenesis of arsenic induced BC should be explored to identify potential markers of clinical importance for better disease management. Arsenic toxicity is a burning health issue along Gangetic belt of West Bengal and higher BC incidence was recorded in affected areas of the state than safe areas. On this background, present hospital-based study aimed to analyse the association of arsenic with development/progression/prognosis of BC in West Bengal and, explore molecular pathogenesis of arsenic-induced BC targeting candidate tumor suppressor genes (TSGs) of chromosome-9 due to previous reports of alteration of the chromosome in BC. In this hospital-based study, majority of BC patients were documented from arsenic affected areas of the state and in these patients, concordantly high tumor arsenic level (AsH, >100 ppb) was detected. High tumor arsenic level was found to be associated with higher proliferation potential (assessed by immunohistochemical analysis of ki67) and pathological stages of tumor and poor patient survival. Thus, in exposed individuals, arsenic accumulates in bladder tissue to influence tumorigenesis and favour acquisition of aggressive tumor phenotypes that affect disease outcome. To explore molecular pathogenesis, 9p22-21 and 9q22.3 were selected based on previous report and candidate TSGs deleted in these regions in AsH tumors were detected by analysing whole genome CGH+SNP array data of our previous study. In 9p22 region, SH3GL2 (SH3 domain containing GRB2 like 2) showed molecular alteration (deletion & promoter methylation) preferably in AsH tumors similar to array based data and, concordant reduced expression. SH3GL2 inactivation seemed to affect receptor mediated endocytosis of active EGFR as evident from overexpression of the later without any amplification of gene in same sample set. SH3GL2 inactivation and associated dysregulation in “negative regulation of ERBB signalling pathway” was seen to have prognostic significance. In 9q22.3 region, deletion, promoter methylation, and concordant reduced expression of PHF2 was seen preferentially in AsH tumors. PHF2 (PHD finger protein 2) involves in “histone lysine (H3K9me2) demethylation pathway” essential for p53 functioning. In present study, PHF2 inactivation might affect p53 mediated transcription as evident from reduced p21 expression in same set of tumors over- expressing p53 protein. CDKN2A and CDKN2B loci from 9p21 region, FANCC and PTCH1 loci from 9q22.3 region were also analysed in this study. As evident from comparable and high frequency of molecular alteration in AsH and AsL (arsenic low; ≤100 ppb) tumors, the gene loci did not seem to have important contribution in pathogenesis of arsenic induced BC. The information on association of arsenic with disease progression, prognosis and related molecular pathogenesis will have implementation in designing preventive and management strategies for arsenic induced bladder cancer in future.
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    Studies on the Protection of Arsenic Induced Reproductive Disorders in Adult Male Wistar Rats by Formulated High Protein Diet
    Mukhopadhyay, Prabir Kumar
    Arsenic toxicity is a major worldwide health problem and has been associated with several reproductive system disorders. The study was designed to investigate the protective role of casein–pea-enriched protein diet /formulated high protein diet (FHPD) on arsenic-mediated testicular and spermatozoal anomalies in adult Wistar rats. The rats (120±10gm) were randomly divided into three groups: Gr I (control) received the normal diet; the Gr II (treated) was given arsenic orally for 30 consecutive days as arsenic trioxide (3mg/kg/rat/day) where as Gr III (supplemented) was given isocaloric FHPD along with arsenic of same dose. Same animal model was used for the fulfilment of all the objectives. The results revealed significant reduction in weight of testis along with other accessory reproductive organs. Structural and functional alterations of testes, cauda epididymis and caudal spermatozoa were observed. Reduction of steroidogenesis, gonadotrophins and spermatogenesis were also noted. Increased oxidative stress resulted redox imbalance in testes, cauda epididymis and spermatozoa causing successive DNA damages. Apoptosis was initiated in testes as expression of apoptotic markers like Bax, Bcl-2, caspase 9 and caspase 3 were seen to be altered. Spermatozoal apoptosis was also noted by Annexin V-Pi staining. Arsenic deposition was also noted in testicular tissues. All these anomalies were attenuated when FHPD supplementation was given to arsenic-gavaged rats. Casein–pea-enriched protein diet/ FHPD mitigated the adverse effects of arsenic and helped in sustaining the normal reproductive functions.