Exam 11: Selective Genetic Sensitivity of Cells to Toxicants

People with polymorphisms in the ALDH1 gene don't enjoy liquor. Why?

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Question 1

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The acetaldehyde they form from ethanol does not get metabolized rapidly to a less toxic form.

How can a CYP polymorphism OR a GSTM polymorphism lead to an increase in toxicity of a compound?

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Increased activation of environmental or industrial toxicant activation (such as PAHs in cigarette smoke) or inability to conjugate toxic metabolites (such as the quinone imine of acetaminophen) may lead to increased toxicity and it may not be clear initially without genetic and metabolic analyses why the person or a specific population responded more strongly to a toxicant or toxicant mixture.

Why would polymorphisms of the OAT1B1 protein lead to liver cell hypersensitivity and polymorphisms of the MRP2 protein lead to liver cell hyposensitivity to the cholesterol lowering drug pravastatin?

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OATP1B1 transported polymorphisms leads to increased plasma concentrations of the metabolite and toxicity of the statins. The opposite is true for those with polymorphisms encoding for a the multidrug resistance-associated protein 2.

Women with the BRCA1 or BRCA2 gene polymorphism/mutation are known to have poor outcomes for prevention of breast cancer. How might alterations of other genes lead to similar prognoses?

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Question 4

Why do people with certain immune gene polymorphisms have dermal toxicity?

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Question 5

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People with polymorphisms in the ALDH1 gene don't enjoy liquor. Why?

How can a CYP polymorphism OR a GSTM polymorphism lead to an increase in toxicity of a compound?

Why would polymorphisms of the OAT1B1 protein lead to liver cell hypersensitivity and polymorphisms of the MRP2 protein lead to liver cell hyposensitivity to the cholesterol lowering drug pravastatin?

Women with the BRCA1 or BRCA2 gene polymorphism/mutation are known to have poor outcomes for prevention of breast cancer. How might alterations of other genes lead to similar prognoses?

Why do people with certain immune gene polymorphisms have dermal toxicity?

Biological Research in Toxicology

Development of the Field of Toxicology

Toxicology Terms and How They Relate to Organisms

Hazard, Exposure, and Risk Modeling

Absorption and Transport of Toxicants Through Membranes: Toxic Damage to Membranes

Receptor-Mediated Toxicities on the Outside of Cells

Detoxication and Activation by Cells: Metabolism of the Original Toxicant

Damage to Cytosolic and Endoplasmic Reticulum Activities

Damage to Mitochondrial and Chloroplast Activities

Damage to Nuclear Structuresdna: Mutagenesis and Carcinogenesis

Nutritional Toxicity and Sensitivity

Routes of Administration and Which Organs Are Most Likely Impacted Based on Route and Toxicokinetic Models

Forensic Toxicity Testing

The Skin and Eye: Most Likely Exposure Routes and Toxicities Due to Contact Exposure and Dose Toxicities

Gastrointestinal System Toxicity and Oral Exposure Gi Tract, Pancreas, Liver

The Lung and Gill Exposures Representing Toxic Concentrationsmodel for Environmental Toxicology

The Cardiovascular System As Conduit for a Dose Becoming a Dosage: Exposure and Toxicities

Bone Marrow and Immune Organ Toxicity Via Lymphatic and Blood Transport

The Nervous System and Exposure to Lipophilic Toxicants or Transported Neurotoxic Agents

Toxicity to Neuroendocrine Organs and Endocrine Disruption

Toxicity to Reproductive Organs and Developmental Toxicity

Excretion of Hydrophilic Toxicants and Metabolites and Kidney Toxicity

Dispersion Modeling in Air, Water, and Soil: Likely Route of Exposure and Most Sensitive Organism Based on Dispersion and Concentration

Agricultural Chemicals Pesticides and Fertilizers: Exposure and Impacts

Industrial Chemicals That Biodegrade: Organic Chemical Exposures and Impacts

Ndustrial Chemicals That Change Lipophilicity but Do Not Biodegrade: Metal Impacts

Industrial Chemicals That Cause Atmospheric Changes and Direct Versus Indirect Toxicity: Gases, Vapors, Aerosols, and Radiation

Toxicity of Pharmaceuticals and Personal Care Products Ppcps Into Water

Venoms and Injection Toxicity Versus Poisonous Animals or Cells and Ingestion or Contact Toxicity

Poisonous Plants or Plant Cells and Ingestion or Contact Toxicity

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