Biomarkers of Lead-Prompted Poisonous quality in Channel Catfish and Human Liver Carcinoma (HepG2) Cells.

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Biomarkers of Lead-Actuated Poisonous quality in Channel Catfish and Human Liver Carcinoma (HepG2) Cells. Paul B. Tchounwou Ecological Toxicology Research Lab, Jackson State College, Jackson, MS, USA Natural Innovation Consortium Washington, D.C. , Walk 10-11, 2003.
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Biomarkers of Lead-Induced Toxicity in Channel Catfish and Human Liver Carcinoma (HepG2) Cells Paul B. Tchounwou Environmental Toxicology Research Laboratory, Jackson State University, Jackson, MS, USA Environmental Technology Consortium Washington, D.C. , March 10-11, 2003

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Background and Rationale Lead is an insignificant component that displays a high level of danger to people It is exceedingly dangerous to kids, and influences essentially every arrangement of the body It can harm a youngster kidneys, and focal sensory system, and reason iron deficiency At abnormal states, lead can bring about extreme lethargies, shakings and demise Even low levels of lead are unsafe

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Background and Rationale Levels as low as 10 ug/dL of blood have been connected with: diminished knowledge conduct issues lessened physical stature and development, and weakened listening to A tyke is assessed to lose 2 IQ focuses for every 10 ug/dL increment in blood lead level Most confirmation of destructive impacts is found in kids whose blood lead levels surpass 10 ug/dL

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Toxicological Profile of Lead Poisoning in Children - - - - - - - Blood Lead Level Adverse Toxicological (ug/dL) Effects - - - - - - - 10 Reduced IQ, hearing, development, conduct issues 20 Impaired nerve capacity 30 Reduced Vitamin D digestion system 42 Damage to blood shaping framework 55 Severe stomach spasms 70 Severe paleness 80 Kidney harm 90 Severe cerebrum harm 130 Death - - - - - - -

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Background and Rationale Most studies with lead have concentrated on its consequences for organ frameworks, for example, the sensory system, the red platelets, and the kidneys which are viewed as the essential focuses of poisonous quality. In any case, little is thought about its unfriendly impacts on the liver and different tissues. The writing is additionally rare with respect to the atomic instruments of lead-actuated poisonous quality in mammalian frameworks.

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Why Channel Catfish ? Oceanic living beings (fish/crayfish) are essential wellsprings of sustenance, and wage for a few occupants Mississippi is No. 1 maker of catfish in the country Contaminated fish may constitute a noteworthy course of human introduction to lead through the natural pecking order

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Research Objectives and Approach To evaluate the intense and ceaseless toxicities of lead to channel catfish ( ictalurus punctatus ) Static restoration bioassays with fish presented to lead nitrate (intense) Flow-through framework bioassays with fish presented to lead nitrate (perpetual) To focus the cytotoxicity of lead MTT measure for cell reasonability with changed human hepatocytes presented to lead nitrate

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Research Objectives and Approach To anticipate the sub-atomic components of lead-instigated danger Gene Profile (CAT-Tox) to survey the transcriptional initiation of anxiety qualities Microarray investigation for extensive scale quality expression To recognize the potential biomarkers of presentation, affectability and impact connected with lead presentation Western Blot and densitometric investigations Histopathological examinations

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Constants: Volume of Water (1.2L) Renewal of Medium (each 24hrs) Time of presentation (96hrs) Number fish (4) No Feeding or Aeration Water Quality: pH Dissolved oxygen Temperature Conductivity Total broke up solids Preliminary Studies

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Water Quality

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Acute Toxicity of Lead to Channel Catfish – 48 hrs Exposure

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Preliminary Findings The centralization of lead has an immediate impact on the death rate of channel catfish. The harmfulness of lead is measurement and time-subordinate. Lead is intensely poisonous to channel catfish

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Cytotoxicity of Lead Nitrate to HepG 2 Cells – 48 hrs Exposure

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Stress Gene Promoter/Response Element-CAT Fusion Constructs - - - - - - - - Promoter Biologic Function - - - - - - - - CYP1A1 Cytochrome-P450 1A1 Phase I biotransformation protein GST Ya Glutathion-s-transferase Phase II biotransformation compound XRE Xenobiotic Resp. Elt. Binding site for Ah-receptor CRE cAMP Response Elt. Binding site for the CREB protein RARE Retinoic Acid RE Binding site for RA HMTIIA Metallothionein Sequestration of overwhelming metals HSP70 Heat Shock Protein Cytoplasmic protein chaperone GRP78 Glucose-Regulated P ER protein chaperone GADD45/153 GA & DNA Damage P Cell cycle regulation FOS c-fos Member of AP-1 TF complex NFkBRE Nuclear Factor Binding site to the NFkB TF p53RE Tumor Suppressor P Binding site for the p53 TF - - - - - - - -

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Deliverables Education and workforce improvement Strengthen educational modules in the territories of natural toxicology and danger appraisal Educate and train under-spoke to understudies in the regions of ecological toxicology and danger evaluation Contribution to science/Research Review and redesign the toxicological profile of lead Identify and clarify the instruments of lead-actuated poisonous quality Scientific distributions ( 3 in 3 years) Scientific presentations ( 6 in 3 years) Faculty advancement in the territory of ecological toxicology and danger appraisal Seminars/workshops/gatherings

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