Chapter 2 - Toxicological Mechanisms Flashcards by Cheryl Fattman

A possible reason for the selective embryo/fetal toxicity of DES is…

A. Higher concentrations of free DES in embryo/fetus compared to adults

B. Binding to retinoic acid receptors

C. Lack of placental metabolism

D. All of the above

A. Higher concentrations of free DES in embryo/fetus compared to adults

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The liver and kidney are major target organs of toxicity because…

A. They both receive a higher percentage of cardiac output

B. They both have substantial xenobiotic metabolizing capacity

C. They both have transport systems that can concentrate xenobiotics

D. All of the above

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Acyl glucuronides are particularly toxic to the liver because…

A. They selectively interact with macrophages releasing active oxygen

B. Active transport systems in the hepatocytes and bile duct system can greatly upconcentrate them

C. They are resistant to glucuronidase

D. They are suicide inhibitors of UGT2B7

B. Active transport systems in the hepatocytes and bile duct system can greatly upconcentrate them

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The selective renal toxicity of cephaloridine over cephalothin is due to…

A. Selective uptake by the organic cation transporter

B. Selective inhibition of P-glycoprotein

C. Selective uptake by the organic ion transporter

D. Significantly less plasma protein binding of cephaloridine

C. Selective uptake by the organic ion transporter

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All of the following are true of alpha-amanitin except…

A. It is less orally available than phalloidin

B. It inhibits RNA polymerase II

C. It is transported into the hepatocyte by a bile acid transporter

D. It is a mushroom toxin

A. It is less orally available than phalloidin

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All of the following are true of the toxic mechanism of paraquat except…

A. Lungs accumulate paraquat in an energy
-dependent manner

B. Its entry into the lung is assumed to be via the polyamine transport system

C. Similar molecules with smaller distances between N atoms do not enter lungs as readily

D. Cytotoxicity to alveolar cells is caused primarily by interference with Ca+2 channels

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Enzyme induction by phenobarbital is mediated through…

A. Aryl hydrocarbon receptors

B. PPAR-alpha receptors

C. Constitutively active receptors (CAR)

D. Estrogen receptors

C. Constitutively active receptors (CAR)

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CAR is downregulated by…

A. Hypericum extracts

B. acetominophen

C. Asprin

D. Proinflammatory cytokines

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The pregnane X receptor…

A. Is a cytosolic receptor

B. Is involved in the induction of Cyp3A4

C. Is primarily expressed in the skin

D. All of the above

B. Is involved in the induction of Cyp3A4

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Xenobiotic toxicity that occurs after repair and adaptive processes are overwhelmed include all of the following except…

A. Fibrosis

B. Apoptosis

C. Necrosis

D. Carcinogenesis

B. Apoptosis

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Amphipathic xeonbiotics that can become trapped in lysosomes and cause phospholipidosis include all of the following except…

A. Ethylene glycol

B. Aminodarone

C. Amitriptyline

D. Fluoxetine

A. Ethylene glycol

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Which of the following parent toxicant-electrophyllic metabolite pairs is incorrect…

A. Halothane-phosgene

B. bromobenzine-bromobenzene 3,4 oxide

C. Benzene-muconic aldehyde

D. Allyl alcohol-acrolein

A. Halothane-phosgene

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All of the following are capable of accepting electrons from reductases and forming radicals except…

A. Paraquat

B. Doxorubicin

C. N-hexane

D. Nitrofurantoin

C. N-hexane

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An example of the formation of an electrophile toxicant from an inorganic chemical is…

A. CO to CO2

B. AsO4-3 to AsO3-2

C. NO to NO2

D. OH to H2O

B. AsO4-3 to AsO3-2

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The general mechanism for the detoxification of electrophiles is…

A. Conjugation with glucuronic acid

B. Conjugation with acetyl CoA

C. Conjugation with glutathione

D. Conjugation with sulfate

C. Conjugation with glutathione

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The most common nucleophilic detoxication reaction that amines undergo is…

A. Acetylation

B. Sulfation

C. Methylation

D. Amino acid conjugation

A. Acetylation

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Detoxication mechanisms may fail because…

A. Toxicants may overwhelm the detoxication mechanims

B. Reactive toxicants may inactivate a detoxicating enzyme

C. Detoxication may produce a toxic by-product

D. All of the above

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The most potent carcinogen derived from nicotine is…

A. Napthene

B. Styrene

C. Nicotine-derived nitrosamine ketone (NNK)

D. Methyl tert-butyl ketone

C. Nicotine-derived nitrosamine ketone (NNK)

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Hydroxyl radicals can be produced by all of the following except…

A. The action of nitric oxide synthase on water

B. Interaction of ionizing radiation and water

C. Reductive homolytic fission of hydrogen peroxide

D. Interaction with silica with surface iron ions in lung tissue

A. The action of nitric oxide synthase on water

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If an electrophile is covalently bound to a protein that does not play a critical function, the result is considered a…

A. Toxication reaction

B. Detoxication reaction

C. DNA adduct formation

D. Fenton reaction

B. Detoxication reaction

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Which of the following receptor-exogenous ligand pairs is incorrect?

A. Estrogen receptor-zeralenone

B. Glucocorticoid receptor - dexamethasone

C. Aryl hydrocarbon receptor - rifampicin

D. PPAR - clofibrate

C. Aryl hydrocarbon receptor - rifampicin

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Which of the following receptor-agonist pairs is incorrect?

A. Glutamate receptor - kainate

B. Glycine receptor - strychnine

C. GABA (A) receptor - muscimol

D. Opioid receptor - meperidine

B. Glycine receptor - strychnine

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Which of the following receptor antagonist pairs is incorrect?

A. Adrenergic B1 receptor - metoprolol

B. Serotonin (2) receptor -ketanserin

C. Glutamate receptor - ketamine

D. GABA (A) receptor - avermectins

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Clonidine overdose mimics poisoning with…

A. Morphine

B. Cocaine

C. Phencyclidine

D. Amphetamine

A. Morphine

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All of the following act as inhibitors of the citric acid cycle except... A. 4-pentenoic acid B. Fluoroacetate C. DCVC D. Malonate

A. 4-pentenoic acid

All of the following are inhibitors of ADP phosphorylation except... A. Oligomycin B. DDT C. Ethanol D. N-ethylmaleimide

C. Ethanol

All of the following cause calcium influx into the cytoplasm except... A. Capsaicin B. Formate C. Domate D. Amphotericin B

B. Formate

All of the following inhibit Ca++ export from the cytoplasm except... A. Vanadate B. Methylmercury C. Bromobenzine D. Carbon tetrachloride

B. Methylmercury

Hydroxyl radical is enzymatically detoxified by.. A. Catalase B. Glutathione peroxidase C. Glutathione reductase D. None of the above

D. None of the above

Which of the following regarding cell death is true? A. Necrosis requires ATP B. Release of cytochrome c usually triggers necrosis C. Toxicants at low doses usually cause apoptosis and necrosis at higher doses D. Apoptosis is never a desirable effect

C. Toxicants at low doses usually cause apoptosis and necrosis at higher doses

Blockade of voltage-gated potassium channels has been demonstrated with all of the following except... A. Cisapride B. Lorazepam C. Terfenadine D. Grepafloxacin

B. Lorazepam

A drug that acts on potassium channels in pancreatic beta cells to impair insulin secretion is... A. Terbutaline B. Niacin C. Diazoxide D. Lidocaine

C. Diazoxide

Chemicals cause major cell death by all of the following mechanisms except... A. Rise in intracellular Ca++ B. ATP depletion C. Inhibition of drug metabolizing enzymes D. Overproduction of ROS

C. Inhibition of drug metabolizing enzymes

All of the following are inhibitors of cytochrome c oxidase except... A. MPP+ B. paraquat C. Azide D. Hydrogen sulfide

A. MPP+

All of the following are inhibitors of NADH coenzyme Q reductase ( complex1) except... A. Rotenone B. Paraquat C. Arsenite D. Amytal

C. Arsenite

All of the following statements are true except.. A. Macrophages can generate NO B. Macrophages can discharge myeloperoxidase into phagocytic vacuoles C. NO radical is produced by the action of NOS on arginine D. Superoxide anion and NO can combine to make peroxinitrite

B. Macrophages can discharge myeloperoxidase into phagocytic vacuoles

A contributing factor in the termination of tissue regeneration is thought to be... A. Depletion of local ATP B. Plateau of protein synthesis regulated by DNA C. Accumulation of hypochlorous acid - an antimitogen D. Dominance of TGFbeta over mitogens

D. Dominance of TGFbeta over mitogens

Overexpression of the divalent metal transporter 1 in iron deficiency will lead to increased intestinal absorption of... A. Cadmium and lead B. sodium and calcium C. Potassium and magnesium D. Lithium and aluminium

A. Cadmium and lead

An intracellular protein that increases ATP production and decreases ATP consumption is... A. ras B. BAX C. AMPK D. VEGF

C. AMPK

The heat-shock and endoplasmicreticulum stress response both... A. Repair damaged DNA B. Repair misfolded proteins C. Repair damaged lipids D. All of the above

B. Repair misfolded proteins

Free radicals can be produced in inflammed tissue by the action of all of the following enzymes except... A. Aconitase B. NADPH oxidase C. Nitric oxide synthase D. Myeloperoxidase

A. Aconitase

All of the following are elements of the hypoxia response except... A. Production of HIF1alpha B. Production of erythropoetin C. Production of proteins that stimulate aerobic ATP synthesis D. Production of growth factors that stimulate angiogenesis

C. Production of proteins that stimulate aerobic ATP synthesis

An example of a protein that results from a mutation of an oncogene is... A. ICAM1 B. ras C. STAT D. C/EBP

B. ras

All of the following are mitogenic growth factors except... A. HGF B. TGFalpha C. CTGF D. Noxa

D. Noxa

If only a few mitochondria are injured in a cell, the outcome ... A. Can be cell survival B. Will always be both cellular apoptosis and necrosis C. Will always be apoptosis D. Will always be necrosis

A. Can be cell survival

Mechanisms opposing distribution of a toxicant to a target tissue include all of the following except... A. Plasma protein binding B. Blood-brain barrier C. Distribution to nontarget organ storage sites D. Cellular uptake transporters on target tissue

D. Cellular uptake transporters on target tissue

Nonvolatile, highly lipid-soluble chemicals that are resistant to bioteansformation are eliminated from the body by all of the following processes except... A. Excretion in the bile B. Excretion in breast milk C. Exhalation D. Intestinal excretion

C. Exhalation

Examples of parent xenobiotics that act as ultimate toxicants include all of the following except... A. Lead B. Carbon tetrachloride C. Tetrodotoxin D. Carbon monoxide

B. Carbon tetrachloride

Examples of xenobiotics whose metabolites act as ultimate toxicants include all of the following except... A. Hexane B. TCDD C. ethylene glycol D. Acetaminophen

B. TCDD

Examples of noncovalent binding of toxicants to target tissues include all of the following except... A. Binding of strychnine to glycine receptors B. Binding of hydroxyl radicals to DNA bases C. Binding of phorbol esters to protein kinase C D. Binding of warfarin to vitamin K 2,3 epoxide reductase

B. Binding of hydroxyl radicals to DNA bases

The binding of hydrogen peroxide with a protein thiol group produces... A. Carbon dioxide and water B. A protein sulfenic acid C. A protein nitrosamine D. Cleavage of the peptide bond

B. A protein sulfenic acid

Major target molecules for toxicants include all of the following except... A. Proteins B. Vitamins C. DNA D. Lipids

B. Vitamins

All of the following toxins act by enzymatic action except... A. Ricin B. Anthrax C. Tetrodotoxin D. Botulinum

C. Tetrodotoxin

Apoptotic pathways can be initiated by... A. DNA damage B. Mitochondrial insult C. Death-receptor stimulation D. All of the above

D. All of the above

The enzyme that repairs oxidized protein thiols is called... A. HMG-coenzyme A reductase B. Adenyl cyclase C. Phospholipase D. None of the above

D. None of the above

The mechanism of action for bleomycin-induced lung injury is presumed to be... A. DNA-adduct formation B. Generation of reactive oxygen species C. Inhibition of cytochrome oxidase D. None of the above

B. Generation of reactive oxygen species

All of the following are true of oxidative DNA damage except... A. Mitochondrial DNA is much more resistant to damage than nuclear DNA B. 8-hydroxy-deoxyguanosine in the urine is a marker C. It can lead to base pair transversions D. It can lead to point mutations

A. Mitochondrial DNA is much more resistant to damage than nuclear DNA

An example of a denatured protein is... A. Golgi complex B. Micronuclei C. Heinz body D. Histone

C. Heinz body

An important feature of lipid peroxidation is... A. It cannot be blocked by antioxidants B. Damage propagated in a chain reaction-like manner C. It never involves the Fenton reaction D. The end products are different from the end products of the reaction of lipids with ozone

B. Damage propagated in a chain reaction-like manner

Which statement is true regarding the PPAR alpha receptor A. Stimulation causes peroxisome proliferation in humans B. They are present in adipose tissue C. They involve fatty acid beta oxidation D. Thiazolidinediones act as ligands

C. They involve fatty acid beta oxidation

Alterations in retinoic acid receptor (RAR) function have been associated with... A. Cardiac and vascular toxicity B. CNS and peripheral nerve toxicity C. Hepatic and renal toxicity D. Embryo and testicular toxicity

D. Embryo and testicular toxicity

Proteins present in brown adipose tissue act mechanistically like... A. Pentachlorophenol B. Rotenone C. Cyanide D. Doxorubicin

A. Pentachlorophenol

Which of the following regarding glutathione is false? A. It can act non-enzymatically as a radical scavenger B. It is a dipeptide C. Its levels can be upregulated in response to a need D. It is a substrate for glutathione peroxidase

B. It is a dipeptide

All of the following are associated with necrosis except... A. Requirement of ATP B. Cell swelling C. Association with an inflammatory response D. Initiation by plasma membrane permeability changes

A. Requirement of ATP

Another name for apoptosis is... A. Passive cell death B. Accidental cell death C. Programmed cell death D. Immune cell death

C. Programmed cell death

A mitochondrial factor involved in the process of apoptosis is... A. Cytochrome a3 B. Cytochrome b6 C. Cytochrome c D. Cytochrome a1

C. Cytochrome c

All of the following are true of apoptosis except... A. Cell membrane remains intact B. Early in the process, caspases are activated C. Oxidative stress can initiate it D. It can lead to carcinogenesis

D. It can lead to carcinogenesis

A class of drugs that can induce apoptosis in certain cancer cells is... A. Barbiturates B. Digitalis glycosides C. Protein pump inhibitors D. COX-2 inhibitors

D. COX-2 inhibitors

Which of the following signal transduction pathway/effect pairs is correct? A. ras/ERK - suppression of apoptosis B. JNK-mediated apoptosis C. p38-production of inflammatory cytokines D. All of the above

D. All of the above

A drug that works by disrupting mitosis is... A. Paclitaxel B. doxorubicin C. Methotrexate D. Cyclophosphamide

A. Paclitaxel

Galactosamine causes... A. Proximal tubular damage B. focal liver necrosis C. Peripheral neuropathy D. All of the above

B. focal liver necrosis

Practolol was withdrawn from use because of... A. Unpredictable beta blockade B. rebound hypertension C. Teratogenicity D. Oculomucutaneous syndrome

D. Oculomucutaneous syndrome

All of the following can inhibit opening of the mitochondrial permeability pore except... A. Cyclosporin A B. hydrophobic bile acids C. L-deprenyl D. Bongkrekic acid

B. hydrophobic bile acids

Microcystins target... A. Adenyl cyclase B. phosphodiesterase C. Protein phosphatase D. Guanyl cyclase

C. Protein phosphatase

All of the following are true of cytokines except... A. Short half-life B. act locally C. Produced in specialized organs D. Have complex interactions

C. Produced in specialized organs

Molecular chaperones... A. Repair denatured proteins B. repair damaged DNA C. repair damaged tRNA D. act as catalysts for new protein synthesis

A. Repair denatured proteins

Lipid repair... A. Cannot occur B. requires NADPH C. May involve catalase D. None of the above

A. Cannot occur

In peripheral neurons with damaged axons, repair... A. Can occur until approx age 5 B. follows the same mechanism as CNS repair C. Requires activated neutrophils and astrocytes D. Requires macrophages and Schwann cells

D. Requires macrophages and Schwann cells

Apoptosis is advantageous in... A. Neoplastic prostate cells B. female germ cells C. Cardiac myocytes D. CNS neurons

A. Neoplastic prostate cells

The principle factor leading to fibrogenesis.. A. IL-8 B. TNFalpha C. TGFbeta D. IL-1

C. TGFbeta

Fibrosis is harmful because... A. It may compress blood vessels B. it may contribute to tissue malnutrition C. It may interfere with mechanical organ function D. All of the above

D. All of the above

All of the following are true regarding idiosyncratic drug reactions except... A. They are rare B. they are predicable from the pharmacology of the drug C. The reaction can be dose independent D. They involve genetic or acquired factors that increase susceptibility

B. they are predicable from the pharmacology of the drug

All of the following would indicate initiation of a cellular stress response except... A. Downregulation of DNA repair enzymes B. induction of apoptosis C. Upregulation of antioxidant mechanisms D. Stimulation of immune response

A. Downregulation of DNA repair enzymes

All of the following contribute to organ-selective toxicity except... A. Organ-selective uptake B. tissue-specific expression of transcription factors C. Number of chromosomes in nucleus D. Tissue-specific receptors

C. Number of chromosomes in nucleus

The nephrotoxic effect of mercury on the kidney is thought to be mediated by... A. Blocking the effect of ADH on the collecting duct B. interfering with ionic charges on the glomerulus C. A dicysteinyl-mercury complex mimicking endogenous cysteine D. Interfering with chloride transport in the loop of Henle

C. A dicysteinyl-mercury complex mimicking endogenous cysteine

An example of a soft neutorphile is... A. Sulfur in glutathione B. phosphate oxygen in nucleic acids C. Mercuric ion D. Carboxylate anion

B. phosphate oxygen in nucleic acids

The Fenton reaction produces... A. Phosgene from chloroform B. formic acid from formaldehyde C. Nitrogen dioxide from ozone and nitrogen D. Hydroxyl radical and hydroxyl ions from hydrogen peroxide

D. Hydroxyl radical and hydroxyl ions from hydrogen peroxide