Biology 4U03 - Exam 1 Fall 2008

Page 1 of 7BIOLOGY 4U03/6U03DAY CLASSA.J. RainbowDURATION OF EXAMINATION: 3 hoursMcMaster University Final ExaminationDecember 2008THIS EXAMINATION PAPER INCLUDES 7 PAGES AND 10 QUESTIONS. YOU ARERESPONSIBLE FOR ENSURING THAT YOUR COPY OF THE PAPER IS COMPLETE.BRING ANY DISCREPANCY TO THE ATTENTION OF YOUR INVIGILATOR.SPECIAL INSTRUCTIONS:All students are to answer all questions in Section A, two (2) questions only from Section Band two (2) questions only from Section C.Please write clearly and neatly in correct grammatical English, and use diagrams wheneverappropriate. State any assumptions you make and show all your working.Use of any calculator is allowed.SECTION A - (Answer all questions)MARKS(1.5)1. (a) Describe briefly how (i) terminal deletions of chromosomes and (ii) dicentricchromosomes arise following exposure of human lymphocytes to ionizing radiation.(2)(b) With the aid of graphs, show the relationship between aberration frequency and dose forboth types of aberration for both x-rays and a-particles at both high and low dose rates.(1.5)(c) Describe briefly an experiment to detect chromosome aberrations in circulating humanlymphocytes and discuss briefly the limitations in the use of chromosome aberrations incirculating human lymphocytes as a method of biological dosimetry.(2)2. (a) Describe what is meant by the Law of Bergonié and Tribondeau, and put the followingtissues in order of increasing sensitivity to ionizing radiation (most resistant first):hemopoietic (bone marrow) tissue, nerve tissue, thyroid epithelium, fine vasculature.(1)(b) Which human tissue type is most sensitive to radiation induced cancer and which humantissue is most resistant to radiation induced cancer.(2)(c) Describe briefly what you understand by the bystander effect as applied to radiationbiology.Continued on next page.. BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 2 of 7MARKS(2)3. (a) Using the Poison distribution, derive a relationship between surviving fraction and dosefor an organism or molecule obeying single-hit, single-target theory. Define clearly anysymbols you use. Under what conditions would you expect survival curves of this shapeto arise following exposure of mammalian cells to ionizing radiation and why?A mammalian cell line, A, has a greater DNA content compared to that of mammaliancell line B. Both show morphologically similar colonies and following exposure to alphaparticles, both cell types exhibit exponential survival according to single-hit, single-targettheory. A mixture of cell type A and type B is irradiated with alpha-particles and assayedfor colony survival, with the following result:Absorbed dose tocell mixture in Gray01234681216202428Percent colonyformation10052342013.55.43.61.851.350.950.70.5Draw the survival curve for colony formation of the composite cells mixture on the semilogarithmic graph paper provided and determine:(1)(b) The Do value for the inactivation of colony formation for cell type B;(1)(c) How much greater is the DNA content of cell type A compared to that of cell type B;(1)(d) What is the ratio of the number of type B cells compared to that of type A cells in theoriginal mixture?(2)4. (a) Using the radiation weighting factors and the tissue weightings factors (given in Tables 1and 2 on page 3), calculate the effective dose for a male radiation worker who hasreceived the following exposures over the past 12 months:20 mGy of 3 Mev alpha-particles to the skin,2 mGy of 50 Kev neutrons, whole body,5 mGy of gamma rays to the stomach and liver,500 mGy of beta particles to the thyroid.Continued on next page... BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 3 of 7Table 1. Radiation weighting factors'Type and energy range2Radiation weighting factor, WPhotons, all energies1Electrons and muons, all energies1Neutrons, energy < 10 keV510 keV to 100 keV10> 100 keV to 2 MeV20> 2 MeV to 20 MeV10> 20 MeV5(See also Figure 1)Protons, other than recoil protons, energy > 2 MeV5Alpha particles, fission fragments, heavy nuclei20Table 2. Tissue weighting factorsTissue or organTissue weighting factor, WTGonads0.20Bone marrow (red)0.12Colon0.12Lung0.12Stomach0.12Bladder0.05Breast0.05Liver0.05Oesophagus0.05Thyroid0.05Skin0.01Bone surface0.01Remainder0.052-MARKS(1.5) 4. (c) What are the current International Commission on Radiological Protection (ICRP)recommended dose limits for occupational exposure to ionizing radiation, which aredesigned to provide protection against both the stochastic and the non-stochastic(deterministic) effects of radiation? Is the individual in part (a) within the recommendeddose limits?(1.5)(d) Give an estimate for the effective dose equivalent and the risk of fatal cancer due toradiation exposure from (i) one chest radiograph taken in a good hospital and (ii) acomputerized tomography examination of the abdomen.Continued on next page BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 4 of 7SECTION B - (Answer only two (2) questions)MARKS(5)5. (a) Give an account of the chemical and biological factors that can influence the survival ofmammalian cells following exposure to ionizing radiation. Indicate clearly how thesurvival is affected by each of the factors you describe and give the underlyingmechanism(s) for the change in each case.A human tumor cell line is irradiated in air and nitrogen with 14-Mev neutrons and innitrogen with 250 kVp x-rays. Survival of cells following radiation is determined usingan in vitro colony assay with the results shown in Table 3, below:Percent clonogenic survivalDose (cGy)Neutron/airNeutron/nitrogenX-ray/nitrogen0100100100606880ND1004062ND200112595300310ND4000.84.380500ND1.767600NDND51800NDND171200NDND10* Not determined(1)(b) Plot the three (3) survival curves on the semi-logarithmic graph paper provided and labelthe curves.(2)(c) Assuming an oxygen enhancement ratio (OER) of 2.4 for exposure of this tumor cell lineto 250 kVp x-rays, draw on the semi-logarithmic paper provided [next to the curvesplotted in 6 (b)], the expected survival curve for exposure of cells to 250 kVp x-rays inthe presence of oxygen. Determine the parameters Dq, Do, D37 and extrapolationnumber, n, for this survival curve.(1)(d) Calculate the OER for 14-Mev neutrons and the Relative Biological Efficiency (RBE) of14-Mev neutrons under anoxic conditions, stating clearly any assumptions you make.(1)(e) A human tumor contains 10 well oxygenated cells only. Use the parameters of theappropriate human tumor cell survival curve above in order to calculate the dose of X-rays required to result in a 90% probability that the tumor is cured.Continued on next page.. BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 5 of 7MARKS(6)6. (a) Give a detailed account of the clinical symptoms, cellular abnormalities and the specificnature of the DNA repair deficiencies at the molecular level in cells from patients withCockayne syndrome, xeroderma pigmentosum and xeroderma pigmentosum variants.Human adenovirus is a double stranded DNA virus with a length of 35 kbp (kilobasepairs) that forms plaques on human fibroblasts. UV irradiation of the virus results in 6 X10-3 thymine dimers/J/m /kbp and following infection of human fibroblasts with UVirradiated adenovirus, one "unrepaired" thymine dimer is sufficient to inactivate theplaque forming ability of the virus. UV irradiated adenovirus is assayed for plaqueforming ability on several different human fibroblast strains.(2)(b) Calculate the Do for plaque forming ability of the virus following infection of a strain ofxeroderma pigmentosum fibroblasts which are unable to repair thymine dimers.(2)(c) Adenovirus is UV-irradiated with a fluence of 190 J/m2 and used to infect humanfibroblasts which are capable of repairing 90% of the UV-induced thymine dimers.Calculate the surviving fraction of plaques after this UV exposure and also the fraction ofadenovirus genomes that contain exactly 2 "unrepaired" thymine dimers.Assume that viral inactivation follows a single-hit, 1 single target survival curve and thatthymine dimers are induced, as well as repaired, at random in the viral DNA. Assumealso that the average number of thymine dimers induced in the viral genome increaseslinearly with UV dose and that the "unrepaired" thymine dimers are the only cause ofUV-induced viral inactivation.(5)7. (a) With reference to the different stages of embryogenesis in mammals, discuss the effectsof radiation on the developing embryo and fetus. Indicate how the possible effects ofradiation are influenced by the stage of embryogenesis at which radiation takes place.Discuss the implications for women radiation workers of reproductive capacity and forthe use of ionizing radiation in medical diagnosis.(5)(b) Describe the method used by the Russell's in their Mega Mouse project to detectradiation-induced recessive mutations in the mouse in the first generation followingexposure to radiation. With reference to gametogenesis (germ line production) inmammals, give an account of the effects of ionizing radiation on germ cell productionand gene mutation in the male and female. Indicate how the effects of radiation areinfluenced by the stage of gametogeneis at which radiation takes place, as well as thedose and dose-rated employed. Discuss the implications for men and women receivingexposure from diagnostic x-rays or other ionizing radiation sources.Continued on next page BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 6 of 7SECTION C - (Answer only two (2) questions)MARKS(5)8. (a) Define or describe briefly what is meant by exposure, absorbed dose, equivalent dose (ordose equivalent) and effective dose (or effective dose equivalent) for ionizing radiation.Give the units in which each is measured and the relationships between these four (4)ways by which the amount of ionizing radiation is measured. Which method ofmeasurement most closely relates to the risk of cancer from the radiation exposure?(3)(b) List the four major components of "natural" background radiation in Canada and give thevalue for the total average annual effective dose equivalent for natural backgroundradiation to the Canadian population. What source of "natural" radiation and what sourceof "man-made" radiation give the greatest contribution to the effective dose equivalent tothe Canadian population?(2)(c) Compare the effective dose received from natural background radiation to that receivedby: (i) radiation workers and (ii) individuals undergoing various medical proceduresinvolving ionizing radiation such as diagnostic radiology and nuclear medicine.(1)9. (a) Define LD50/ and give its value in humans following whole body exposure to ionizingradiation.(3)(b) Discuss the factors affecting the LD50/30 in mammals following whole body exposure toionizing radiation, indicating how the LD50/30 is affected by each factor you discuss.(6)(c) Describe the three radiation syndromes for humans following acute whole body exposureto ionizing radiation. Indicate for each syndrome, the signs and symptoms, thedisturbance in cellular kinetics that leads to death, the mean survival time, the doses ofradiation involved and the possible methods of treatment.(3)10. (a) With reference to named examples describe how the concept of oncogenes and tumorsuppressor genes provides a model for the mechanisms of cancer induction by radiation.(4)(b) Give an account of the carcinogenic effects of ionizing radiations. Discuss the data fromexposed human populations as well as that from animal and tissue culture experimentsgiving the magnitude of the radiation doses for the data you describe.(3)(c) Discuss the evidence that the linear non-threshold model for radiation induced cancermight (i) overestimate and (ii) underestimate the carcinogenic risk of ionizing radiation tothe human population at low doses.Continued on next page BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 7 of 7TABLE OF CONSTANTSAvogardo's number (# molecules in the gram molecular weight) = 6.023 X 1023A solution at a concentration of 1 M = the gram molecular weight in 1 liter1 ev=1.6 X 10-12 ergs1 erg=6.24 X 10 ev1 Joule=10 ergse-0.1=0.9e-1=0.367e-1.6=0.2e-2=0.135e 3=0.05log 1.4=0.3333log. 2=0.693log. 2.72=1log .10=2.3The End 10 MM/CM 10 MM CM