Midterm Flashcards
Deithylstilbestrol (DES) exposure:
increases the risk of clear cell adenocarcinoma of the vagina.
Early (prenatal) exposure to which of the following teratogens is most often characterized by craniofacial dysmorphism?
ethanol.
The nervous system is derived from which of the following germ layers?
ectoderm.
Toxin exposure during which of the following periods is likely to have the LEAST toxic effect on the developing fetus?
preimplantation.
Regarding prenatal teratogen exposure, which of the following statements is FALSE?
a. Major effects include growth retardation and malformations.
b. Exposure to teratogens during critical developmental periods will have more severe effects on the fetus.
c. There is considered to be a toxin level threshold below which the fetus is capable of repairing itself.
d. The immune system of the fetus is primitive, so the fetus has little to no ability to fight off chemicals and repair itself.
e. Embryo lethality becomes more likely as the toxic dose is increased.
d. The immune system of the fetus is primitive, so the fetus has little to no ability to fight off chemicals and repair itself.
What stages of the cell cycle are important in monitoring DNA damage and inhibiting progression of the cell cycle?
G1-S, S, G2-M
What molecule is NOT important in determining the ultimate outcome of embryonal DNA damage?
a. p53.
b. Bax.
c. Bcl-2.
d. c-Myc.
e. NF- κB.
e. NF- κB.
What is NOT a physiologic response to pregnancy?
a. increased cardiac output.
b. increased blood volume.
c. increased peripheral vascular resistance.
d. decreased plasma proteins.
e. increased extracellular space.
c. increased peripheral vascular resistance.
All of the following statements are true EXCEPT:
a. Offspring of white mothers have a higher incidence of cleft lip or palate than do black mothers, after adjusting for paternal race.
b. Cytomegalovirus (CMV) is a common viral cause of birth defects.
c. Folate supplementation during pregnancy decreases the risk of neural tube defects.
d. Cigarette smoke and ethanol are both toxic to the placenta.
e. In humans, there is a negative correlation between stress and low birth weight.
e. In humans, there is a negative correlation between stress and low birth weight.
Which of the following is NOT a mechanism involving the endocrine system by which chemicals induce developmental toxicity?
a. acting as steroid hormone receptor ligands.
b. disrupting normal function of steroid hormone metabolizing enzymes
c. disturbing the release of hormones from the hypothalamus.
d. disturbing the release of hormones from the pituitary gland.
e. elimination of natural hormones.
e. elimination of natural hormones.
What cell types secretes anti-Müllerian hormone (AMH)?
Sertoli cell.
Penile erections are dependent on:
corpora cavernosa smooth muscle relaxation.
The corpus luteum is responsible for the secretion of which of the following hormones during the first trimester?
progesterone and estradiol.
All of the following statements regarding the hypothalamo-pituitary-gonadal axis are true EXCEPT:
a. FSH increases testosterone production by the Leydig cells.
b. FSH and LH are synthesized in the anterior pituitary.
c. Estradiol provides negative feedback on the hypothalamus and the anterior pituitary.
d. GnRH from the hypothalamus increases FSH and LH release from the anterior pituitary.
e. The LH spike during the menstrual cycle is responsible for ovulation.
a. FSH increases testosterone production by the Leydig cells.
Which of the following statements is FALSE regarding gametal DNA repair?
a. DNA repair in spermatogenic cells is dependent on the dose of chemical.
b. Spermiogenic cells are less able to repair damage from alkylating agents.
c. Female gametes have base excision repair capacity.
d. Meiotic maturation of the oocyte decreases its ability to repair DNA damage.
e. Mature oocytes and mature sperm no longer have the ability to repair DNA damage
e. Mature oocytes and mature sperm no longer have the ability to repair DNA damage.
Reduction division takes place during the transition between which two cell types during spermatogenesis?
primary spermatocyte and secondary spermatocyte.
Which of the following cell types is properly paired with the substance it secretes?
a. ovarian granulosa cells - progesterone
b. Leydig cells – ABP.
c. ovarian thecal cells – estrogens.
d. Sertoli cells – testosterone.
e. gonadotroph – LH
e. gonadotroph – LH
Which of the following statements regarding male reproductive capacity is FALSE?
a. Klinefelter’s syndrome male are sterile.
b. FSH levels are often measured in order to determine male reproductive toxicity of a particular toxin.
c. Divalent metal ions, such as AN, Hg, and Cu, act as androgen receptor antagonists and affect male reproduction.
d. The number of sperms produced per day is approximately the same in all males.
e. ABP is an important biochemical marker for testicular injury
d. The number of sperms produced per day is approximately the same in all males.
Reduction of sperm production can be caused by all of the following diseases EXCEPT:
a. hypothyroidism.
b. measles.
c. Crohn’s disease.
d. renal failure.
d. mumps.
b. measles.
Of the following, which is LEAST likely to be affected by estrogen?
a. nervous system.
b. musculoskeletal system.
c. digestive system.
d. cardiovascular system.
e. urinary system.
c. digestive system.
There is evidence that certain dietary components are carcinogenic. What is NOT tabbed as a dietary carcinogen?
insufficient caloric intake
Which of the following statements regarding mechanisms of chemical carcinogenesis is FALSE?
a. Procarcinogens require metabolism in order to exert their carcinogenic effect.
b. Free radicals are highly reactive molecules that have a single, unpaired electron.
c. DNA adducts interfere with the DNA replication machinery.
d. Mutations in the DNA and failure to repair those mutations can be highly carcinogenic.
e. Biological reduction of molecular oxygen is the only way free radicals can be formed.
e. Biological reduction of molecular oxygen is the only way free radicals can be formed.
In addition to being necessary for transcription to occur, what transcription factor also plays a crucial role in nucleotide excision repair?
TFIIH
Which of the following statements regarding DNA repair is TRUE?
a. Base excision repair requires the removal of a longer piece of DNA in comparison with nucleotide excision repair.
b. The repair of double-stranded DNA breaks is more prone to error than is base excision repair.
c. Dimerization of pyrimidines is required via base excision repair.
d. Mismatch repair can only recognize normal nucleotides that are paired with a noncomplementary nucleotide.
e. Nucleotide excision and base excision are tolerance mechanisms used to respond to DNA damage.
b. The repair of double-stranded DNA breaks is more prone to error than is base excision repair.
What is a characteristic of the initiation stage of carcinogenesis?
Cell division is required for the fixation of the process.
Tumor suppressor genes are mutated in a majority of cancers. Which of the following is NOT a characteristic of a tumor suppressor gene?
a. A mutation in a tumor suppressor gene is dominant.
b. Germ line inheritance of a mutated tumor suppressor gene is often involved with cancer development.
c. There is considerable tissue specificity for cancer development.
d. The p53 gene is a tumor suppressor gene that also acts as a transcription factor.
e. Mutations in tumor suppressor genes can result in loss of cell cycle control.
a. A mutation in a tumor suppressor gene is dominant.
Which of the following molecules does NOT play an important role in cell cycle regulation?
a. p53
b. cyclin-D
c. MAPK
d. MHC
e. E2F
d. MHC
Which of the following environmental factors is proportionally responsible for the LEAST amount of cancer deaths?
a. tobacco
b. infection
c. diet
d. sexual behavior
e. alcohol
e. alcohol
The evidence of the carcinogenicity of dietary intake is sufficient to include one’s diet as associated with neoplasms of all of the following EXCEPT:
a. colon
b. breast
c. pancreas
d. endometrium
e. gallbladder
c. pancreas
What is the correct definition of a complete carcinogen?
A chemical possessing the ability of inducing cancer from normal cells, usually possessing properties of initiating, promoting, and progression agents
Five identical experimental animals are treated with 1 mg of one of the following toxins. The animal treated with which toxin is most likely to die?
a. ethyl alcohol (LD50 = 10,000 mg/kg)
b. botulinum toxin (LD50 = 0.00001 mg/kg)
c. nicotine (LD50 = 1 mg/kg)
d. ferrous sulfate (LD50 = 1500 mg/kg)
e. picrotoxin (LD50 = 5 mg/kg)
b. botulinum toxin (LD50 = 0.00001 mg/kg)
Place the following mechanisms of toxin delivery in order from most effective to least effective:
1: intravenous
2: subcutaneous
3: oral
4: inhalation
5: dermal
1, 4, 2, 3, 5
A toxin with a half-life of 12 h is administered every 12 h. Which of the following is true?
b. The concentration of the chemical in the body will slowly increase until the toxic concentration is attained.
Urushiol is the toxin found in poison ivy. It must first react and combine with proteins in the skin in order for the immune system to recognize and mount a response against it. Urushiol is an example of what?
hapten
Toxic chemicals are most likely to be transformed in which of the following organs?
liver
When chemicals A and B are administered simultaneously, their combined effects are far greater than the sum of their effects when given alone. The chemical interaction between chemicals A and B can be described as which of the following?
synergistic
With respect to dose-response relationships, which of the following is true?
Quantal dose-response relationships allow for the analysis of a population’s response to varying dosage.
When considering the dose-response relationship for an essential substance:
Adverse responses increase in severity with increasing or decreasing dosages outside of homeostatic range.
The therapeutic index of a drug:
Describes the ratio of the toxic dose to the therapeutic dose of a drug.
Penicillin interferes with the formation of peptidoglycan cross-links in bacterial cell walls, thus weakening the cell wall and eventually causing osmotic death of the bacterium. Which of the following is true?
Treatment with penicillin is a good example of selective toxicity.
Which of the following is NOT important in hazard identification?
a. structure-activity analysis
b. in vitro tests
c. animal bioassays
d. susceptibility
e. epidemiology
d. susceptibility
The probability of an adverse outcome is defined as:
risk
The systematic scientific characterization of adverse health effects resulting from human exposure to hazardous agents is the definition of:
risk assessment
Which of the following is NOT an objective of risk management?
a. setting target levels for risk
b. balancing risks and benefits
c. calculating lethal dosages
d. setting priorities for manufacturers
e. estimating residual risks
c. calculating lethal dosages
Which of the following is NOT a feature in the design of standard cancer bioassays?
a. more than one species
b. both sexes
c. near lifetime exposure
d. approximately 50 animals per dose group
e. same dose level for all groups
e. same dose level for all groups
Which type of epidemiologic study is always retrospective?
case-control
What is defined as the highest nonstatistically significant dose tested?
NOAEL
What represents the dose below which no additional increase in response is observed?
threshold
Which of the following is NOT needed to calculate the reference dose using the BMD method?
a. MF
b. percent benchmark response
c. NOAEL
d. UF
e. benchmark dose
c. NOAEL
Virtually safe doses are described at which confidence level?
95%
Biotransformation is vital in removing toxins from the circulation. All of the following statements regarding biotransformation are true EXCEPT:
a. Many toxins must be biotransformed into a more lipid-soluble form before they can be extracted from the body.
b. The liver is the most active organ in the biotransformation of toxins.
c. Water solubility is required in order for many toxins to be excreted by the kidney.
d. The kidney plays a major role in eliminating toxicants from the body.
e. The lungs play a minor role in ridding the body of certain types of toxins.
a. Many toxins must be biotransformed into a more lipid-soluble form before they can be extracted from the body.
Which of the following statements about active transport across cell membranes is FALSE?
a. Unlike simple of facilitated diffusion, active transport pumps chemicals against an electrochemical or concentration gradient.
b. Unlike simple diffusion, there is a rate at which active transport becomes saturated and cannot move chemicals any faster.
c. Active transport requires the expenditure of ATP in order to move chemicals against electrochemical or concentration gradients.
d. Active transport exhibits a high level of specificity for the compounds that are being moved.
e. Metabolic inhibitors do not affect the ability to perform active transport.
e. Metabolic inhibitors do not affect the ability to perform active transport.
What might increase the toxicity of a toxin administered orally?
increased dilution of the toxin dose
What most correctly describes the first-pass effect?
Orally administered toxins are partially removed by the GI tract before they reach the systemic circulation.
What is an important mechanism of removing particulate matter from the alveoli?
absorption into the bloodstream, followed by excretion via the kidneys.
For a toxin to be absorbed through the skin, it must pass through multiple layers in order to reach the systemic circulation. What is the most important in slowing the rate of toxin absorption through the skin?
stratum corneum.
A toxin is selectively toxic to the lungs. What mode of toxin delivery would most likely cause the LEAST damage to the lungs?
intraperitoneal.
Which of the following is NOT an important site of toxicant storage in the body?
a. adipose tissue.
b. bone.
c. plasma proteins.
d. muscle.
e. liver.
d. muscle.
Which of the following regarding the blood-brain barrier is TRUE:
a. The brains of adults and newborn are equally susceptible to harmful blood-borne chemicals.
b. The degree of lipid solubility is a primary determinant in whether or not a substance can cross the blood-brain barrier.
c. Astrocytes play a role in increasing the permeability of the blood-brain barrier.
d. Active transport processes increase the concentration of xenobiotics in the brain.
e. The capillary endothelial cells of the CNS possess large fenestrations in their basement membranes.
b. The degree of lipid solubility is a primary determinant in whether or not a substance can cross the blood-brain barrier.
Which of the following will result in DECREASED excretion of toxic compounds by the kidneys?
a. a toxic compound with a molecular weight of 25,000 Da.
b. increased activity of the multidrug-resistance (mdr) protein.
c. increased activity of the multiresistant drug protein.
d. increased activity of the organic cation transporter.
e. increased hydrophilicity of the toxic compound.
d. increased activity of the organic cation transporter.
Xenophobic biotransformation is performed by multiple enzymes in multiple subcellular locations. Where would one of these enzymes most likely NOT by located?
a. cytosol.
b. Golgi apparatus.
c. lysosome.
d. mitochondria.
e. microsome.
b. Golgi apparatus.
All of the following statements regarding hydrolysis, reduction, and oxidation biotransformations are true EXCEPT:
a. The xenobiotic can be hydrolyzed.
b. The xenobiotic can be reduced.
c. There is a large increase in hydrophilicity.
d. The reactions introduce a functional group to the molecule.
e. The xenobiotic can be oxidized.
c. There is a large increase in hydrophilicity.
What is often conjugated to xenobiotics during phase II biotransformations?
sulfate group
Which of the following is a true statement about the biotransformation of ethanol?
a. Alcohol dehydrogenase is only present in the liver.
b. Ethanol is reduced to acetaldehyde by alcohol dehydrogenase.
c. Ethanol and hydrogen peroxide combine to form acetaldehyde with the aid of catalase.
d. In spite of its catalytic versatility, cytochrome P450 does not aid in ethanol oxidation.
e. Acetaldehyde is oxidized to acetic acid in the mitochondria by aldehyde dehydrogenase.
e. Acetaldehyde is oxidized to acetic acid in the mitochondria by aldehyde dehydrogenase.
What enzyme is responsible for the biotransformation and elimination of serotonin?
monoamine oxidase
Which of the following reactions would likely NOT be catalyzed by cytochrome P450?
a. dehydrogenation.
b. oxidative group transfer.
c. epoxidation.
d. reductive dehalogenation.
e. ester cleavage.
e. ester cleavage.
All of the following statements regarding cytochrome P450 are true EXCEPT:
a. Poor metabolism or biotransformation of xenobiotics is often due to a genetic deficiency in cytochrome P450.
b. Cytochrome P450 can be inhibited by both competitive and noncompetitive inhibitors.
c. Certain cytochrome P450 enzymes can be induced by one’s diet.
d. Increased activity of cytochrome P450 always slows the rate of xenobiotic activation
e. Induction of cytochrome P450 can lead to drug tolerance
d. Increased activity of cytochrome P450 always slows the rate of xenobiotic activation
Which of the following statements regarding phase II biotransformation (conjugation) reactions is true?
a. Phase II reactions greatly increase the hydrophilicity of the xenobiotic.
b. Phase II reactions are usually the rate-determining step in the biotransformation and excretion of xenobiotics.
c. Carboxyl groups are very common addition of phase II reactions.
d. Most phase II reactions occur spontaneously.
e. Increased phase II reactions result in increased xenobiotic storage in adiopocytes.
a. Phase II reactions greatly increase the hydrophilicity of the xenobiotic.
Where do most phase II biotransformations take place?
cytoplasm
Which of the following is NOT an important co-substrate for phase II biotransformation?
a. UDP-glucoronic acid.
b. 3’-phosphoadenosine-5’-phosphosulfate (PAPS).
c. S-adenosylmethionine (SAM).
d. N-nitrosodiethylamine.
e. acetyl CoA
d. N-nitrosodiethylamine.
SELECT ALL THAT APPLY: The Phase II reaction(s) whose rates are limited by cofactor availability is/are:
a. Glucuronidation
b. Sulfonation
c. Methylation
d. Acetylation
e. Glutathione conjugation
a. Glucuronidation
b. Sulfonation
e. Glutathione conjugation
The Phase II reaction occurring in the brain believed to be responsible for producing a metabolite 600x more potent than morphine is:
glucuronidation
SELECT ALL THAT APPLY: The Phase II reaction(s) that tend(s) to favor conjugation to all the heteroatoms: O, N, S is/are:
a. Glucuronidation
b. Sulfonation
c. Methylation
d. Acetylation
e. Glutathione conjugation
a. Glucuronidation
c. Methylation
e. Glutathione conjugation
SELECT ALL THAT APPLY: The Phase II reaction(s) that generally decrease(s) resultant metabolite water solubility is/are:
a. Glucuronidation
b. Sulfonation
c. Methylation
d. Acetylation
e. Glutathione conjugation
c. Methylation*
d. Acetylation*
The Phase II reaction that generally possesses the highest concentration of cofactor is:
glutathione conjugation
The Phase II reaction(s) that exhibits [a] very significant genetic polymorphism(s), specifically in isoniazid metabolism, is
acetylation
SELECT ALL THAT APPLY: The amino acids used as substrates in the conjugation of carboxylate-containing xenobiotics are:
a. glycine
b. glutamine
c. taurine
d. serine
e. proline
a. glycine
b. glutamine
c. taurine
SELECT ALL THAT APPLY: The amino acids used as substrates in the conjugation of aromatic hydroxylamine-containing xenobiotics are:
a. glycine
b. glutamine
c. taurine
d. serine
e. proline
d. serine
e. proline
The severity of a toxin/toxicant depends, in large part, on the concentration of the toxin/toxicant at its site of action. Which of the following will decrease the amount of toxin/toxicant reaching its site of action?
a. Absorption across the skin
b. Excretion via the kidneys
c. Metabolic activation
d. Reabsorption across the intestinal mucosa
e. Discontinuous endothelial cells of hepatic sinusoids
Excretion via the kidneys
Metabolic activation (toxication) is the biotransformation of a toxin/toxicant to a more toxic or reactive species. Which of the following is NOT a reactive chemical species commonly formed by metabolic activation (toxication)?
a. Electrophiles
b. Nucleophiles
c. Superoxide anions
d. Hydroxy radicals
e. Hydrophilic organic acids
Hydrophilic organic acids
Which of the following is NOT an important step in the detoxification of chemicals?
a. Formation of redox-active reactants
b. Reduction of hydrogen peroxide by glutathione peroxidase
c. Formation of hydrogen peroxide by superoxide dismutase
d. Reduction of glutathione disulfide (GSSG) by glutathione reductase (GR)
e. Conversion of hydrogen peroxide to water and molecular oxygen by catalase
a. Formation of redox-active reactants
Regarding the interaction of the ultimate toxicant with its target molecule, which of the following is FALSE?
a. Toxins often oxidize or reduce their target molecules, resulting in the formation of a harmful by-product
b. The covalent binding of a toxin with its target molecule permanently alters the target’s function
c. The noncovalent binding of a toxin to an ion channel irreversibly inhibits ion flux through the channel
d. Abstraction of hydrogen atoms from endogenous compounds by free radicals can result in the formation of DNA adducts
e. Several toxins can act enzymatically on their specific target proteins
c. The noncovalent binding of a toxin to an ion channel irreversibly inhibits ion flux through the channel
All of the following are common effects of toxicants on target molecules EXCEPT:
a. Blockage of neurotransmitter receptors
b. Interference with DNA replication due to adduct formation
c. Cross-linking of endogenous molecules
d. Opening of ion channels
e. Mounting of an immune response
d. Opening of ion channels
What protein functions to prevent the progression of the cell cycle?
IκB
What would have the largest negative impact on intracellular ATP levels?
b. Interference with electron delivery to the electron transport chain
What happens when a toxin/toxicant induces elevation of cytosolic calcium?
Mitochondrial uptake of calcium dissipates the electrochemical gradient needed to synthesize ATP.
Cytochrome c is an important molecule in initiating apoptosis in cells. All of the following regarding cytochrome c are true EXCEPT:
a. The release of cytochrome c into the cytosol is an important step in apoptosis initiation.
b. The loss of cytochrome c from the electron transport chain blocks ATP synthesis by oxidative phosphorylation
c. Loss of cytochrome c from the inner mitochondrial membrane results in increased formation of reactive oxygen species
d. Bax proteins mediate cytochrome c release
e. Caspases are proteases that increase cytosolic levels of cytochrome c
e. Caspases are proteases that increase cytosolic levels of cytochrome c
Which of the following is NOT associated with carcinogenesis?
a. Mutation
b. Normal p53 function
c. Ras activation
d. Apoptosis inhibition
e. DNA repair failure
b. Normal p53 function
Which molecule determines whether a toxicant damaged cell undergoes necrosis or apoptosis?
ATP
SELECT ALL THAT APPLY: The insertion of the mitochondrial permeability transition pore (MPTP) complex is mediated by:
a. The activation of the adenine nucleotide translocase subunit
b. A significant change in the voltage across the inner mitochondrial membrane
c. A significant change in the voltage across the outer mitochondrial membrane
d. A significant increase in the amount of free Ca2+ within the mitochondrial matrix
e. A high mitochondrial inner membrane potential
b. A significant change in the voltage across the inner mitochondrial membrane
d. A significant increase in the amount of free Ca2+ within the mitochondrial matrix
DNA insult, such as a double stranded DNA break, directly activates __, an important nucleic, pro-apoptotic signaling molecule.
p53
During the process of lipid peroxidation, lipid hydroperoxide (LOOH) is converted to the highly reactive lipid alkoxyl radical (LO-) via
Fenton Reaction
The mitochondrial protein that is released into the cytosol upon mitochondrial membrane potential dissipation triggering the intrinsic apoptotic pathway via binding to Apaf-1 and ATP is:
Cytochrome c
Cytochrome c specifically cleaves which procaspase into its active form:
Procaspase 9
