1) An employee working in a nuclear power plant is accidentally exposed to a total body γ-ray dose of 2 Gy. Ten days after the accident, you draw blood and submit it for hematologic analysis. Which of the following would you expect to see?
A. A drop in hemoglobin concentration and platelet counts.
B. A drop in platelet count and an increase in lymphocyte count.
C. A drop in lymphocyte count but no effect on hemoglobin concentration.
D. An increase in the number of neutrophils but no effect on hemoglobin concentration.
E. No effect on lymphocytes, hemoglobin, neutrophils or platelets.
2) A terrorist preparing a “dirty bomb” containing 210Po received a total body dose equivalent of approximately 8 Sv resulting from an accidental ingestion of this radioisotope. He did not seek medical attention and died 7 days later from acute radiation toxicity. Which of the following would you expect to see at autopsy?
A. bone marrow aplasia
B. mitotic arrest of intestinal crypt cells
C. cerebral edema
D. microvasculitis
E. necrosis of neurons
3) Which of the following pairs of total body radiation effects and approximate threshold dose is CORRECT?
A. gastrointestinal syndrome – 2 Gy
B. LD50 (no medical intervention) – 3.5 Gy
C. LD50 (best current medical treatment) – 15 Gy
D. cerebrovascular syndrome – 5 Gy
E. hematopoietic syndrome – 0.2 Gy
4) The death of a person 30-60 days following a total body radiation dose close to the LD50 would likely be due to damage to the:
A. heart
B. bone marrow
C. central nervous system
D. brain
E. gastrointestinal system
5) The prodromal radiation syndrome following total body irradiation:
A. is not seen unless doses exceed 10 Gy
B. occurs after the exposed person has recovered from the GI syndrome
C. can be ameliorated through treatment with amifostine approximately 3-5 hours after the exposure
D. includes GI symptoms such as anorexia, nausea and vomiting that occur within minutes to hours following exposure and lasting hours to days, depending on the radiation dose
E. is characterized by hematopoietic system damage, but no effects related to the gastrointestinal system
6) Following a total body dose of 12 Gy, an exposed individual will not show the bone marrow syndrome because:
A. higher doses than 12 Gy are needed to cause the bone marrow syndrome
B. the individual will likely die within 5-16 days from the GI syndrome, before overt symptoms of the bone marrow syndrome occur
C. this dose is not sufficiently high to cause any radiation syndrome
D. a bone marrow transplant will likely have been given and would mask the symptoms of the bone marrow syndrome
E. at this dose the prodromal syndrome will be so severe it will overshadow the bone marrow syndrome
7) Based on experience with bone marrow transplants performed in individuals accidentally exposed to radiation, it has become evident that the transplants are only useful when the radiation dose to the exposed person is within a narrow window. That window is:
A. 1-2 Gy
B. 3-4 Gy
C. 8-10 Gy
D.15-20 Gy
E. bone marrow transplants have no usefulness at any dose
8) Which of the following statements concerning the effects of radiation on the heart is CORRECT?
A. Pericarditis is the main manifestation of radiation-induced heart disease among radiotherapy patients.
B. In the absence of concurrent chemotherapy, cardiomyopathy is observed during or shortly after the completion of radiotherapy.
C. An increased incidence of cardiovascular disease among Hodgkin’s disease survivors who received mediastinal radiotherapy has not been observed.
D. The critical structure associated with the pathogenesis of radiation-induced heart disease appears to be the endothelial lining of blood vessels.
E. An excess relative risk for myocardial infarction has been detected in the Japanese atomic bomb survivors, but only among those who received doses greater than 10 Gy.
9) All of the following normal tissue complications are of concern after localized, high-dose irradiation of bony structures, EXCEPT:
A. osteoradionecrosis
B. stress fractures
C. growth retardation after irradiation of epiphyseal plates in children
D. radiation-induced bone sarcomas
E. bone marrow failure
10) Common manifestations of delayed anorectal radiation toxicity include all of the following, EXCEPT:
A. intestinal obstruction
B. bleeding
C. intermittent incontinence
D. pain
E. urgency
11) Clinical radiation esophagitis presents as dysphagia or a substernal burning sensation with acute esophagitis seen some 2 weeks after the start of radiation therapy. One clinical approach to treat this complication is the use of:
A. angiotensin converting enzyme inhibitors (ACEIs) such as captopril
B. gene therapy with MnSOD
C. non-steroidal anti-inflammatory agents (NSAIDs)
D. pentoxifylline
E. vitamin C
12) Irradiating bone leads to loss of osteoblasts and osteoclasts responsible for bone maintenance and remodeling, causing the bone to become brittle and prone to injury. Although the incidence of bone injury has decreased since the advent of megavoltage radiotherapy and improved planning and delivery techniques, bone injury can still occur. One type of bone injury is mandibular radionecrosis (MORN). Which of the following is NOT a risk factor for MORN?
A. presence of teeth
B. pre-existing dental disease
C. use of fluorinated water
D. tooth extraction after radiotherapy
E. use of large doses per fraction during treatment
13) Which of the following types of blood cells is most radioresistant?
A. granuocyte/monocyte colony forming cells (GM-CFC)
B. spleen-colony forming units (CFU-S)
C. macrophages
D. unprimed T-helper cells
E. B-cells
14) What portion of the gastrointestinal tract generally exhibits the greatest acute radiation-induced injury for a given dose?
A. stomach
B. oropharynx
C. small intestine
D. large intestine
E. esophagus 53
15) Which of the following statements concerning radiation-induced damage to the eye is TRUE?
A. The threshold X-ray dose for a radiation-induced cataract is approximately 10 Gy.
B. It is often possible to distinguish a radiation-induced cataract from an age-induced one.
C. The neutron RBE for cataract formation is about 5 for low total doses.
D. The tolerance dose for the production of blindness is lower than for cataract formation.
E. The length of the latency period for cataract formation is independent of radiation dose.
16) Which of the following statements is TRUE concerning radiation effects on the bone marrow?
A. In general, B cells are more radiosensitive than T cells.
B. Following total body irradiation, thrombocytopenia is typically observed before neutropenia.
C. Lymphocyte counts do not drop until several weeks after total-body irradiation.
D. Individuals suffering from the bone marrow syndrome usually die of severe anemia.
17) Which of the following statements is CORRECT concerning the effects of radiation on the gonads?
A. Older women are more sensitive to radiation-induced sterility than younger women.
B. An acute dose of 3 Gy can both destroy the gametogenic epithelium and eliminate the production of sex hormones in adult men.
C. Spermatids and spermatozoa are quite radiosensitive whereas spermatogonia are relatively radioresistant.
D. A minimum waiting period of 5 years is recommended for both men and women before attempting procreation following radiotherapy, in order to reduce the risk of radiation-induced genetic effects.
E. If sterility in the male is not produced within the first month after the start of radiotherapy, it is unlikely to ever occur.
18) When administered after a course of radiotherapy, which of the following agents is LEAST likely to reduce the incidence or severity of late effects in normal tissues?
A. antioxidant such as vitamin C
B. ACE inhibitor such as captopril
C. anti-TGF-β1 antibody such as 1D11
D. superoxide dismutase mimetic such as carnosine
E. anti-VEGF antibody such as bevacizumab
19) With respect to radiation-induced toxicity in the lung, which of the following statements is FALSE?
A. The severity of the injury is highly dependent on the volume irradiated.
B. A characteristic pulmonary late effect, radiation pneumonitis, typically arises about 6-12 months following the completion of radiotherapy.
C. The dose response curve for lung injury following whole lung irradiation is steep regardless of the dose per fraction used.
D. Lung toxicity is enhanced when radiation is combined with many different types of chemotherapy.
E. Several cell types are involved in the development of pulmonary late effects, including the type II pneumocyte, the alveolar macrophage and vascular endothelial cells.
20) The oral mucosa and skin present with many similar pathological features during their progression toward radiation toxicity. Which of the following statements is FALSE regarding the overlapping pathologies observed in these tissues?
A. Oral mucositis is a result of the death and consequent desquamation of the epithelial layers, and is therefore an equivalent event to the radiodermatitis (dry/moist desquamation) seen as an early response in irradiated skin.
B. Erythema secondary to vasodilation is observed in skin following doses greater than about 2 Gy, similar to the case for mucositis.
C. Radiation effects in both oral mucosa and skin are dependent on total dose, fraction size and volume irradiated.
D. Possible late effects in both skin and oral mucosa include ulceration and fibrosis.
E. The development of dental caries following oral radiotherapy is similar mechanistically to the infections that accompany radiation-induced dermal ulcers; both result from ischemic necrosis due to the loss of small blood vessels.
21) With respect to radiation-induced heart disease (RIHD), which one of the following statements is FALSE?
A. The highest risk for coronary artery disease is seen in young women (≤20 years of age) and those over about 65 years of age.
B. The parietal pericardium is a cardiac tissue that may be damaged by radiation therapy, with the injury typically presenting as an increased thickness of the fibrous layer.
C. The risk of pericarditis increases with increasing dose per fraction.
D. The majority of cardiac complications observed are consistent with the hypothesis that the most radiosensitive cells are the cardiomyocytes.
E. Cardiac effects are described as “delayed”, and typically appear months to years after radiotherapy.
22) With respect to the morphologic changes associated with radiation-induced liver disease, notably veno-occlusive disease (VOD), all of the following may be observed, EXCEPT:
A. heavy congestion in the sinusoids
B. atrophy of the liver plates
C. fiber-filled lumen of the sublobular veins
D. apoptotic Kupffer cells filled with hematoxylin
E. subacute morphological changes
23) Which of the following statements regarding radiation-related inflammatory effects is FALSE?
A. Following radiation injury, the extent of neutrophil infiltration into the irradiated volume is positively correlated with the severity of the late complication.
B. A distinct inflammatory phase is a major component of many acute tissue reactions.
C. In both experimental animals and humans, late infiltrations of activated macrophages have been noted in irradiated tissues such as lung and oral mucosa.
D. Total body irradiation to doses of 1 Gy or more can lead to abnormalities in T cell immunity.
E. There is evidence that the apoptotic index among T lymphocytes after irradiation can be used as a predictor of subsequent tissue injury.
24) Which of the following cytokines is generally considered both anti-inflammatory and immunosuppressive?
A. Interleukin 1
B. Interleukin 6
C. Interleukin 8
D. Interleukin 10
E. Tumor necrosis factor alpha (TNFα)
25) Studies with laboratory animals have shown that all of the following interventions can reduce lethality after total body irradiation, EXCEPT:
A. fuid and electrolyte therapy
B. inhibitors of poly(ADP-ribose) polymerase (PARP)
C. antibiotics
D. probiotics
E. blood product administration
26) With regard to the retreatment tolerance of previously-irradiated normal tissues, which of the following statements is FALSE?
A. The lung is capable of extensive long-term recovery after doses that are below the tolerance dose for radiation pneumonitis.
B. Re-irradiation tolerance for acute damage in rapidly-dividing mucosal tissues is generally observed.
C. The spinal cord is capable of moderate long-term recovery after irradiation.
D. Re-irradiation tolerance of the kidney increases with increasing time interval between treatments, indicating continuous repair of sub-threshold damage.
E. The onset of late bladder damage occurs much earlier in animals that were re-irradiated following a low sub-tolerance intital radiation dose, as opposed to being treated to tolerance in a single course of therapy.
27) Which of the following statements concerning radiation-induced late effects is TRUE?
A. Most late effects develop as a result of the killing of endothelial cell clonogens.
B. Most late effects are due to the loss of parenchymal cell clonogens.
C. Radiation-induced late effects produce unique pathological responses.
D. The development of late effects shares many elements in common with both acute and chronic wound-healing responses in normal tissues.
E. Once present, late effects are irreversible.
28) With regard to the latency period for the expression of radiation-induced normal tissue injury, which of the following statements is CORRECT?
A. The latency period for early-responding tissues decreases markedly with increasing radiation dose.
B. Shortening the overall treatment time by accelerating radiotherapy reduces the latency period for early-responding tissues.
C. Shortening the overall treatment by accelerating radiotherapy increases the latency period for late-responding tissues.
D. The higher the total radiation dose, the shorter the latency period for late-responding tissues.
E. The latency period for early-responding tissues depends on the rate of vascular endothelial cell turnover.
29) The development and progression of radiation-induced late effects is thought to involve, at least in part, acute and chronic inflammation. Evidence in support of this hypothesis includes all of the following, EXCEPT:
A. Irradiating the kidney leads to a marked and persistent infiltration of inflammatory cells.
B. Ionizing radiation increases the expression of adhesion molecules, including E-Selectin and ICAM1.
C. Ionizing radiation activates the pro-inflammatory transcription factors NF-κB and AP-1.
D. Irradiating the brain leads to acute and chronic microglial activation.
E. Lung irradiation is associated with the presence of activated macrophages in the irradiated volume.
30) With regard to radiation-induced changes in cytokines and growth factors, which of the following statements is CORRECT?
A. The radiation-induced increase in inflammatory cytokines and growth factors has been linked mechanistically to late normal tissue morbidity.
B. The pattern of increases in cytokines observed following irradiation of normal tissues is tissue-independent.
C. There is little difference in the pattern of radiation-induced changes in cytokine production whether the total dose was delivered singly or as a series of small dose fractions.
D. Lack of tumor necrosis factor receptors is associated with an increase in the severity of radiation-induced brain injury.
31) Radiation effects on the nervous system typically arise as a consequence of damage to:
A. axons
B. neurons
C. oligodendrocytes and glial cells
D. the perikaryon
E. dendrites
32) Which of the following statements is TRUE concerning irradiation of the salivary glands?
A. Serous acinar cells die only by mitotic catastrophe after irradiation.
B. The serous acinar cells of the parotid and submaxillary glands are considered the target cells for radiation-induced salivary gland damage.
C. Salivary dysfunction is a late radiation effect rarely observed earlier than six months following treatment.
D. Mucous cells are more radiosensitive than serous cells.
E. Dose fractionation results in significant sparing of serous cells.
33) Which statement concerning TGF-β1 (TGFB1) and bFGF (FGF2) is TRUE?
A. The pro-fibrotic activities of TGF-β1 are mediated by SMAD3.
B. Stimulation of TGF-β1 synthesis should improve the therapeutic ratio.
C. bFGF has been shown to sensitize endothelial cells to radiation-induced apoptosis.
D. Loss of TGF-β1 diminishes the ATM-mediated DNA damage stress response
E. The level of TGF-β1 typically decreases following lung irradiation.
34) Regarding radiation fibrosis, which of the following statements is TRUE?
A. Fibrosis occurs in only a select few tissues and organs.
B. The severity of late fibrosis can be predicted based on radiotherapy treatment parameters and is not tissue-dependent.
C. Radiation fibrosis is typically inhomogenous; some affected areas could be densely collagenous whereas others may have only a few fibrous bands, despite both areas receiving the same dose.
D. Irradiated bone marrow commonly develops regions of fibrosis.
E. Increases in collagen deposition are due to the down-regulation of fibrogenic cytokines, such as TGF-β1 (TGFB1).
35) Both molecular and cellular responses occur as a result of irradiation. Which of the following statements regarding these responses is FALSE?
A. Some mammalian cells are hypersensitive to very low radiation doses (0.01 – 0.3 Gy).
B. Damage to either the cell membrane or DNA can lead to the transcription of early response genes.
C. Radiation damage modifies the expression of stress-related kinases and transcription factors, affecting such activities as cell cycle progression and DNA repair.
D. Normal cells respond to radiation damage by delaying progression through the cell cycle, principally during the G2 phase.
E. There is an immediate increase in the expression of both pro-inflammatory and fibrogenic cytokines after irradiation, followed by a gradual decline during the latency period prior to the clinical manifestation of radiation injury.
