Biology 4U03 - Exam 1 Fall 2006

StudentNameBIOLOGY 4U03/6U03NumberDAY CLASSA.J. RainbowDURATION OF EXAMINATION: 3 hoursMcMaster University Final ExaminationDecember 2006THIS EXAMINATION PAPER INCLUDES 5 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 SectionB and two (2) questions only from Section C.Please write clearly and neatly in correct grammatical English, and use diagramwhenever appropriate. State any assumptions you make and show all your working.Use of any calculator is allowed.MARKSSECTION A(1.5) 1. (a) What are the various 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?(1)(b) What is the average annual Effective Dose Equivalent of ionizing radiation to amember of the Canadian population. What source of "natural" radiation and whatsource of "man-made" radiation gives the greatest contribution to the effective doseequivalent to the Canadian population?(1.5)(c) Define or describe briefly what is meant by the indirect effect of ionizing radiationWhat are thought to be the important reactive chemical species which mediate thiseffect following x-ray exposure of biological tissue? What is the time period betweenwhen radiation enters a cell and the indirect effect of radiation is complete?(1)(d) Describe briefly the operation of a ferrous sulphate (Fricke) dosimeter. Include in yourdescription an indication of the measurementswhich are made following irradiation ofthe dosimeter and how they relate to radiation dose.continued on next page BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 2 of 5MARKS(2).2.(a) Describe briefly how you would obtain an in vivo survival curve following gamma-rayexposure for a named mammalian cell type. Draw the survival curve you would expectand give a typical value for the D37 value of the curve.(1.5)(b) Describe briefly what you understand by the bystander effect as applied to radiationbiology.(1.5)(c)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 (marrow) tissue, muscle tissue, thyroid epithelium, fine vasculature tissue.(1.5) 3. (a) Using the Poisson distribution, derive the mathematical relationship between survivingfraction and dose for the inactivation of cells which follow single-target, single hittheory. Define all the symbols you use.(0.5)(b) Under what conditions would mammalian cell survival curves of this general shapearise following exposure to ionizing radiation?(3)(c) A rapidly dividing suspension cultured of mammalian cells is in logarithmic growthsuch that their number double each day. When the cell concentration is 10 cells/ml, asample of the culture is taken and irradiated with 1.25 Gray of ionizing radiation withthe following effect on cell growth:Day of irradiationCell concentration (x 10 cells/ml)No. dose1.25 Gray01.01.012.01.024.01.238.01.5416.03.0532.06.0664.012.07ND23.08ND45.09ND88.010NDFrom a graph of cell concentration (log) plotted against time, find the fraction of cellswhich retain the ability for continued division after this dose (semi-log graph paper isprovided).Assuming the colony survival curve for these cells following the radiation exposure issimple exponential, calculate graphically (or otherwise) the D. value for the survivalcurve, and the dose in rads of this type of radiation required each day to hold thenumber of viable cells (cell capable of continued division) at the constant level.continued on next page BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 3 of 5MARKS(1)4. (a) What is the most abundant type of DNA lesion resulting from exposure of human cellsto (i) ionizing radiation, (ii) UV-C ultraviolet light, and (iii) the chemical carcinogenmitomycin C.(1)(b)Name a human genetic disease that displays a marked increase in sensitivity to (i)ionizing radiation, (ii) UV-C ultraviolet light, and (iii) the chemical carcinogenmitomycin C.(3)(c) For each of these three diseases, give the clinical symptoms and the deficiency at themolecular level that leads to the increased sensitivity.SECTION B(4)5. (a)Give an account of two physical and two chemical factors which influence the shape ofsurvival curves for mammalian cells following ionizing radiation. Indicate clearly howthe survival curve is affected by each of the factors you describe and give theunderlying mechanism(s) for the change in each case.(2)(b) State the mathematical equation for a multi-target, single-hit, survival curve. Definethe parameters Dq, Do, D37 and extrapolation number for such a survival curve andgive the two mathematical equations which show how these parameters are related.A human tumor cell line is irradiated in air or under anoxic conditions with either 250kVp X-rays or 14-Mev neutrons. The survival curves obtained follow multi-target,single-hit theory with the following parameters:Survival curve parametersDoD37Dqextrapolation(rads)(rads)(rads)numberX-rays (anoxic)7502.4X-rays (air)140Neutrons (anoxic)60Neutron (air)608(1)(c) Calculate the extrapolation number for neutron irradiation and the D37 value forirradiation with X-rays in air.(1)(d) Calculate the oxygen enhancement ratio for both X-rays and 14-Mev neutrons.(1)(e) Calculate the relative biological effectiveness (RBE) for 14-Mev neutrons under anoxicconditions.(1)(f) A human tumor contains 109 well oxygenated cells only. Use the parameters of cellsurvival curve of X-rays (air) to calculate the absorbed dose of X-rays required to resultin a 90% probability that the tumor is cured (e-01 = 0.9; e-1 = 0.367).continued on next page BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 4 of 5MARKS(1)6. (a) What is the magnitude of the doubling dose (in Sievert) for genetic mutations inhumans following acute exposure to ionizing radiation?(4)(b) Describe the experiment used in the Russell's Mega Mouse Project to detect recessivemutations in the mouse in the first generation following exposure to ionizing radiation.How are such mutations effected by the stage of gametogenesis at which radiation takesplace and the dose rate of the radiation, in both the male and the female? Discuss theimplications of the above for individuals of child bearing age who may be exposed toionizing radiation.(3)(c) Describe briefly how (i) terminal deletions of chromosomes and (ii) dicentricchromosomes arise following exposure of human lymphocytes to ionizing radiationWith the aid of graphs, show the relationship between aberration frequency and dosefor both types of aberration for both x-rays and alpha-particles at both high and lowdose rates.(2)(d) Describe an experiment to detect the presence of chromosome aberrations in circulatinghuman lymphocytes and discuss briefly the limitations in the use of chromosomeaberrations in circulating human lymphocytes as a method of biological dosimetry.(2)7. (a) Give the risk estimates (nominal probability coefficients) for cancer lethality inducedby ionizing radiation according to the current recommendations of the InternationalCommission of Radiological Protection. Explain why these risk estimates differ forlow dose, low dose-rate compared to high dose, high dose-rate and for the wholepopulation compared to a working population.(2)(b)With reference to named examples, describe how the concepts of oncogenes and tumorsuppressor genes provide a model for the mechanism of cancer induction by ionizingradiation.(6)(c) Give a detailed account of the carcinogenic effects of ionizing radiations. Discuss thedata from exposed human populations as well as that from animal and tissue cultureexperiments giving the magnitude of the doses for the data you describe. What are thelimitations of the available data in assessing the carcinogenic risk to the humanpopulation from chronic low dose exposure to ionizing radiation.continued on next page BIOLOGY 4U03/6U03 (McMaster University Final Examination)Page 5 of 5SECTION CMARKS8.Give a detailed account of the repair of ionizing radiation induced damage in mammals.Include in your answer the details of experiments which give evidence for repair ofradiation damage in terms of:(3)(a) Removal of DNA damage(3)(b) Enhanced cell survival and(2)(c) The response of tissues after local exposure(2)(d) What is the evidence that some repair mechanisms may only be induced in cells after asufficient amount of radiation damage?(1)9. (a) Define LD50/60 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 bodyexposure to ionizing radiation. Indicate for each syndrome, the signs and symptoms,the disturbance in cellular kinetics which leads to death, the mean survival time, thedoses of radiation involved and the possible methods of treatment.(2)10. (a) Describe briefly what is meant by nucleotide excision repair of DNA.(3)(b) Describe an experiment to determine the relative amount of nucleotide excision repairoccurring in transcriptionally active versus transcriptionally inactive mammalian cellDNA following UV irradiation of cells.(5)(c)Give an account of the human genetic diseases which arise from deficiencies innucleotide excision repair. Describe the clinical symptoms, the cellular and molecularabnormalities, including the defective gene(s) for each of the diseases you describe.THE END