第七章射線的生物學(xué)效應(yīng)等演示文稿

第七章射線的生物學(xué)效應(yīng)等演示文稿本文檔共313頁；當(dāng)前第1頁；編輯于星期三\9點(diǎn)33分輻射生物學(xué)效應(yīng)輻射劑量應(yīng)用放射治療輻射育種輻射保鮮輻射殺蟲、滅菌本文檔共313頁；當(dāng)前第2頁；編輯于星期三\9點(diǎn)33分CellsFourconcepts(collectivelyknownascelltheory):thecellisthebasicstructuralandfunctionalunitoflivingorganisms-definingcellpropertiesdefineslifetheactivityofanorganismisdependentonboththeindividualandcollectiveactivitiesofitscellsaccordingtotheprincipleofcomplementarity,thebiochemicalactivitiesofcellsaredeterminedandmadepossiblebyspecificsubcellularstructurescontinuityoflifehasacellularbasisThehumanbodyhas~50-60trillioncells本文檔共313頁；當(dāng)前第3頁；編輯于星期三\9點(diǎn)33分ChemicalConstituencyofCellsWaterProteins蛋白質(zhì)

-aminoacidchains氨基酸鏈Carbohydrates碳水化合物

-sugars,starches,etc.;Cx(H2O)Nucleicacids-DNA,RNALipids-fatsSalts-NaClandKCl本文檔共313頁；當(dāng)前第4頁；編輯于星期三\9點(diǎn)33分IdealizedSchematicofaCellTwomajorsections:cytoplasmandnucleus本文檔共313頁；當(dāng)前第5頁；編輯于星期三\9點(diǎn)33分圖2—4動(dòng)物細(xì)胞亞顯微結(jié)構(gòu)示意圖圖2—3植物細(xì)胞亞顯微結(jié)

構(gòu)示意圖本文檔共313頁；當(dāng)前第6頁；編輯于星期三\9點(diǎn)33分Cytoplasm細(xì)胞質(zhì)Cytoplasmcellularmaterialinsidetheplasmamembraneandoutsidethenucleusthesiteofmostmetabolicfunctionsofthecell:anabolism(buildingup)andcatabolism(breakingdown)oforganiccompoundsconsistsofthreemajorelements:Cytosol細(xì)胞液-viscoussemitransparentfluidthatsuspendstheorganelleswithinthecytoplasmOrganelles細(xì)胞器

-membraneboundstructuresthatcompartmentalizethecytoplasmandallowthecelltooperateinahighlyorganizedmannerInclusions-chemicalsubstancessuchaslipiddropletsormelaningrains(notpresentinallcells;notfunctioningunits)本文檔共313頁；當(dāng)前第7頁；編輯于星期三\9點(diǎn)33分TheCellNucleusLargestorganelle(~5mmdia.)thickermembraneandmoreviscousfluidContainsthenucleolus核仁andchromatin染色質(zhì)

Gene-containingcontrolcenterthecellbrainregulatescellularprocessesMostcellscontainonenucleus,however,someareanucleate(nonucleus)-redbloodcellscannotreproduce;dieafterafewmonthsmulti-nucleate(severalnuclei)-skeletalmusclecells本文檔共313頁；當(dāng)前第8頁；編輯于星期三\9點(diǎn)33分Chromosomes染色體Genes（基因）Chromatin（染色質(zhì)）DNALife’sBuildingBlocks本文檔共313頁；當(dāng)前第9頁；編輯于星期三\9點(diǎn)33分DNADNA(deoxyribonucleicacid脫氧核糖核酸)isacoileddouble-helicalpolymer（聚合體）(strandsofproteinsandsugars)ThebaseunitofDNAiscalledthenucleotide（核苷酸）composedofadeoxyribose-sugarmoleculeslinkedtoaphosphategroup(adenine,guanine,cytosine,thymine)本文檔共313頁；當(dāng)前第10頁；編輯于星期三\9點(diǎn)33分DNAandChromatinSolenoidNucleosomeDNAH1CoreParticlechromatiniscomposedofnearlyequalamountsofDNAandglobular（球狀）histone（組蛋白）proteinshistonesprovideaphysicalmeansofpackagingtheDNAmoleculeinaverycompactandorderlyway;playsimportantroleingeneregulation本文檔共313頁；當(dāng)前第11頁；編輯于星期三\9點(diǎn)33分LevelsofDNAcondensationDNAdouble-strandhelix.Chromatinstrand(DNAwithhistones).Condensedchromatinduringinterphase（間期）withcentromere（著絲點(diǎn)）.Condensedchromatinduringprophase.(TwocopiesoftheDNAmoleculearenowpresent)Chromosomeduringmetaphase.本文檔共313頁；當(dāng)前第12頁；編輯于星期三\9點(diǎn)33分ChromosomedetailsItisdifficulttoappreciatedetailsofchromosomestructureevenwithanelectronmicroscope.However,onelabelthemwithdyesthatarepreferentiallytakenupbycertainregionsThesemodificationscreateabandingpatternthatcanbeusedtoidentifyandcharacterizeindividualchromosomes.本文檔共313頁；當(dāng)前第13頁；編輯于星期三\9點(diǎn)33分DNAandChromosomesTounderstandhowtheDNAandhistonesareorganizedinachromosome,wemustappreciatethefactthatthenucleusisonly6micrometersindiameter.ThetotallengthofDNAinthehumangenomeis1.8meters.Thus,inordertopacktheDNAintothenucleusasinthephotographofthemetaphasechromosome,theremustbeseverallevelsofcoilingandsupercoiling.Thereisnearlya10,000-foldreductioninlengthinaninterphasenucleus.Eachchromosomecontains1longmoleculeofDNAplusassociatedhistones(basicproteins)whichhelpinthecondensationandregulationprocesses.本文檔共313頁；當(dāng)前第14頁；編輯于星期三\9點(diǎn)33分ChromosomeOrganizationDifferentlevelsofuncoilinginthechromosomeareshown.4nmDNAfilamentsarelabeledthe"DNAhelix".DoublestrandedDNAiswrappedaroundsetsof8histonestoforma10nmfilament.Setsof8histoneswrappedbyDNAareseparatedbyspacerregionsof4nmDNAfilament(doublestrandedDNA)andHistoneH1.arecalled"nucleosomes".Nnextlevelofcoilingproduces30nmnucleoproteinfibersFurtherloopingofnucleoproteinfibersaroundaproteinscaffoldformstheindividualmetaphasechromosomes本文檔共313頁；當(dāng)前第15頁；編輯于星期三\9點(diǎn)33分GenesTheunitofgeneticmaterialresponsiblefordirectingcytoplasmicactivityandtransmittinghereditaryinformationEachgenecontainsafinitesectionofDNAwithspecificbasesequencecodingEachgenesoccupiesaspecificchromosomallocus本文檔共313頁；當(dāng)前第16頁；編輯于星期三\9點(diǎn)33分ChromosomesEachchromosomecontainsmanygenesarrangedinaspecificlinearsequenceConstrictedatcertainpointsbyacentromere,aclearregionnecessaryformovementofthechromosomeduringcelldivisionChromosomesareconstantinnumberforeachspecies本文檔共313頁；當(dāng)前第17頁；編輯于星期三\9點(diǎn)33分RelativeSizesofGeneticMaterials本文檔共313頁；當(dāng)前第18頁；編輯于星期三\9點(diǎn)33分TheCellLifeCycleTheseriesofchangesacellgoesthroughfromthetimeitisformeduntilitreproducesisitslifecycleThelifecycleiscomprisedoftwomajorperiods:Interphase間期cellgrowsandcarriesonitsusualactivitiesMitosis有絲分裂(mitoticphase)cellularreproduction本文檔共313頁；當(dāng)前第19頁；編輯于星期三\9點(diǎn)33分TheCellCycle本文檔共313頁；當(dāng)前第20頁；編輯于星期三\9點(diǎn)33分InterphaseThe“growthphase”;preparingfornextdivisionTotalperiodfromcellformationtocelldivisionDuringInterphasethechromosomalmaterialisseenintheformofdiffusechromatinInterphaseisdividedintoG1,S,andG2sub-phases:G1-(1stgrowthperiod)cellssynthesizeproteinsandgrowvigorouslyS-(synthesis)replicationofDNAG2-(2ndgrowthperiod)enzymes酶/proteinsneededfordivisionaresynthesizedandmovedtotheirpropersites本文檔共313頁；當(dāng)前第21頁；編輯于星期三\9點(diǎn)33分DNAReplicationSphaseMustoccurbeforedivision,sothatidenticalcopiesofthecell’sgenescanbepassedonProcessincludes:anenzymeuncoils,untwistsandseparatestheDNAmoleculeintotwocomplementarynucleotide核苷酸chainstwoidenticalstrandsofDNAresulteachstrandhashalfoftheoldDNAmoleculeandhalfisnewlysynthesized本文檔共313頁；當(dāng)前第22頁；編輯于星期三\9點(diǎn)33分MitosisCelldivisionDividedintofourdistinctphases:prophase(earlyandlate)metaphaseanaphase

telophase(andcytokinesis)本文檔共313頁；當(dāng)前第23頁；編輯于星期三\9點(diǎn)33分TheCommonTheoryofBiologicalDamageResultingfromRadiationExposure本文檔共313頁；當(dāng)前第24頁；編輯于星期三\9點(diǎn)33分Review-EnergyLossbychargedparticlesHeavychargedparticleslosekineticenergyviaasequenceofsmallenergytransferstoatomicelectronsinthemedium.Mostenergydepositionoccursintheinfratrack,anarrowregionaroundtheparticletrackextendingabout10atomicdistances.Ionizationoutsidetheinfratrackiscausedbyveryenergeticparticlesthatescapefromtheinfratrackandsecondaryelectrons.Themoreenergeticinteractionsejectelectronsfromtheirparentatomsandgenerateprimaryion-pairs.AnapproximateexpressionforthemaximumenergytransfertoanelectronfromaheavychargedparticleofmassnumberAandenergyE(MeV)isgivenby:Wmax=215E/AwhereWmaxisineV.Thussecondaryelectronsgeneratedbya5MeValphaparticlerangeuptoabout300eVofkineticenergy.本文檔共313頁；當(dāng)前第25頁；編輯于星期三\9點(diǎn)33分EnergyLossbychargedparticlesEnergeticsecondarye’scaninitiateadditionalionizations,whilelessenergeticonesinduceelectronicexcitations.Lowestenergysecondarye’sarereferredtoas"sub-excitation",whoseroleinbiologicalradiationdamageremainsunclear.Onlyasmallfractionofinitialenergyistransferredateachevent,atrackconsistingofclustersofionsorspursisgeneratedalongthepathofthemovingparticle.Mostspursinwatercomprise1-5ion-pairs.Thesetracksmaybevisualizedinacloudchamberbytheirvaportrail.High-energysecondaryelectronsareoccasionallygenerated.Energylossbytheseenergeticelectronsleadstoshortbranchingtracksor"deltarays"Deltaraysmayterminateinlargerpear-shapedregionsofionisationor"blobs".Similarconsiderationsapplyforenergytransfertoafluidmediuminindirectaction.本文檔共313頁；當(dāng)前第26頁；編輯于星期三\9點(diǎn)33分EnergyLossbychargedparticlesSpursandexcitationsinthetrackofanalpha-particleinwater.Eachcircledepictsanionizationorexcitationevent.Thebranchingtracksare"deltarays".100Angstrom本文檔共313頁；當(dāng)前第27頁；編輯于星期三\9點(diǎn)33分DistributionofIon-pairsinwaterfrompassageoffastelectronsandbetaparticlesFastelectrons&betasloseenergybyinelasticcollisionswithelectronsofthemedium.Electronstracksarelessdensethanthetracksofheavychargedparticles,owingtothelowerLET,andthespursaremorewidelyspacedwithmorefrequentdeltaraysterminatingwithblobs.Onlyabout20%ofbetaparticlespenetratetothemaximumrangeowingtotheirbroadenergydistribution.Inadditiontoenergydeposition,electronsundergoelasticelectron-electroncollisionsleadingtomultiplescatteringandcurvatureofthetrackswhichcomplicatethedosimetryinextendedsources本文檔共313頁；當(dāng)前第28頁；編輯于星期三\9點(diǎn)33分Shorttracks>5000eV<5000eVPrimarypathSpurs100to500eVblobs<100eVDeltaRaysBranchtracksIonpaircreationinwaterfromSecondaryElectrons本文檔共313頁；當(dāng)前第29頁；編輯于星期三\9點(diǎn)33分DirectandIndirectActionBiologicaleffectsofradiationresultprincipallyfromdamagetotheDNADNAisthe“criticaltarget”Targetcanreceivedirectdamagedbyphysicalinteractionwithradiation,orindirectdamagedbyfreeradicalsformedwhenradiationinteractswithwatermoleculesinthecell本文檔共313頁；當(dāng)前第30頁；編輯于星期三\9點(diǎn)33分DirectActionPhysicalinteractionthatdirectlyionizestheDNAmoleculeDNAdamageresultsfromthephysicalbreakageofchemicalbondswithintheDNAbackboneNucleotidebonds,phosphatebondsorstrandbreaksmayresultfromradiationdamageThisdamagemayormaynotberepairable本文檔共313頁；當(dāng)前第31頁；編輯于星期三\9點(diǎn)33分IndirectActionH2O+hn-->H2O++e--->H?+?OHChemicalinteractionsH2O+isanion(charged)electronejectedfromthewatermolecule?OHisthehydroxyradicalafreeradicalhasanunpairedelectronfromabrokencovalentbondandisveryreactivemustbeincloseproximitytoDNAtodoitsdamagebychemicalreaction本文檔共313頁；當(dāng)前第32頁；編輯于星期三\9點(diǎn)33分DirectandIndirectAction:

Neutrons本文檔共313頁；當(dāng)前第33頁；編輯于星期三\9點(diǎn)33分DirectandIndirectAction:

PhotonsIndirectActionDominantforLowLETRadiation本文檔共313頁；當(dāng)前第34頁；編輯于星期三\9點(diǎn)33分EnergyAbsorptioninRadiobiologyEnergyisabsorbed,butdamageisdonebybreakingchemicalbondsEnergydepositedincellsandtissuesunevenlyindiscretepacketsaverageabsorptionperionizingevent~34eVtypicalC=Cbindingenergy4.9eVremaindergoesintootherionization,excitation,andbiologicaldamage本文檔共313頁；當(dāng)前第35頁；編輯于星期三\9點(diǎn)33分TimeScaleofEventsInitialionization:~10-15secFree-ionlifetime:~10-10secFree-radicallifetime:~10-5secBreakageofbondsandexpressionofbiologicaleffectscelldeath:hourstodaysoncogenesis:yearsgermcellmutation:generations本文檔共313頁；當(dāng)前第36頁；編輯于星期三\9點(diǎn)33分ClassicParadigmofRadiationInjury←1s→←min-hrs→←days→←weeks→←months→←years→←generations→IonizingRadiationDNADamageCellDeathDNAMutationHeritableEffectsCancerDevelopmentaleffects(fetal)LateeffectsChemicalRepair(ionsrecombine)Ionizations(freeradicalformation,etc)ExcitationsHeatEnzymaticDNARepairEarly(Acute)Effects(Radiationsickness)本文檔共313頁；當(dāng)前第37頁；編輯于星期三\9點(diǎn)33分DNAStrandBreaksDNAcansuffersingleanddoublestrandbreaksStrongcircumstantialevidencethatDNAisprincipaltargetforcellkillingAsingle-strandbreakoccurswhenonlyoneofthehelicessuffersabreakAdouble-strandbreakoccurswhenbothhelicessufferabreakeitherdirectlyoppositeoneanotherorwhenseparatedbyonlyafewbasepairs本文檔共313頁；當(dāng)前第38頁；編輯于星期三\9點(diǎn)33分DiagramofsingleanddoublestrandDNAbreaksGGGGCCCCAAATTT2nmBlob7nmdiameter,12ionpairsSpur4nmdiameter,3ionpairs本文檔共313頁；當(dāng)前第39頁；編輯于星期三\9點(diǎn)33分DiagramofsingleanddoublestrandDNAbreaksGGGGCCCCAAATTTSinglestrandbreak本文檔共313頁；當(dāng)前第40頁；編輯于星期三\9點(diǎn)33分DiagramofsingleanddoublestrandDNAbreaksGGGGCCCCAAATTTWellseparateddoublestrandbreak本文檔共313頁；當(dāng)前第41頁；編輯于星期三\9點(diǎn)33分DiagramofsingleanddoublestrandDNAbreaksGGGCCCCAAATTTAdjacentdoublestrandbreakGGGGCCCAAATTT本文檔共313頁；當(dāng)前第42頁；編輯于星期三\9點(diǎn)33分Single-StrandBreaksReadilyrepairedusuallydoesnotleadtomutationsorcelldeathImproperrepairispossiblenormallyleadstomutationsordeath本文檔共313頁；當(dāng)前第43頁；編輯于星期三\9點(diǎn)33分Double-StrandBreaksDifficultorimpossibletorepairmayleadtoprogrammedcelldeath(apoptosis),mutationorcarcinogenesisIfnotrepaired,orrepairisinerror,mutationsmaybereplicatedmayleadtocellsthatfunctionimproperlyandhaveunregulatedcellgrowth(e.g.,cancer)本文檔共313頁；當(dāng)前第44頁；編輯于星期三\9點(diǎn)33分FragmentBehavior(post-break)RepairbreaksmayrejoinintheiroriginalconfigurationAberrationbreaksmayfailtorejoinbrokenendsmayrejoinotherbrokenends,etcoccursatnextmitosis本文檔共313頁；當(dāng)前第45頁；編輯于星期三\9點(diǎn)33分ChromosomalAberrationsOftencausedbybreakageandincorrectrejoiningbrokensegmentsmayremainseparatedfromminutestohours;endsaresaidtobe“sticky”theyarecapableofreattachingtoanyotherbrokensegments(mostoftenrejoiningintheiroriginalconfiguration)breaksduringspecificphasesofmitosisresultindifferentendpoints(aswewillsee)本文檔共313頁；當(dāng)前第46頁；編輯于星期三\9點(diǎn)33分Radiation-InducedAberrationsOccurwhencellisirradiatedbeforethechromosomematerialhasbeenduplicatedFrequencyofsingle-strandbreaksincreaseslinearlywithradiationdoseFrequencyofdouble-strandbreaksincreaseswithdoseasapowerfunction(powerof~1.5to2)本文檔共313頁；當(dāng)前第47頁；編輯于星期三\9點(diǎn)33分Radiation-InducedAberrationsDose-rateeffectforsingle-strandbreakslowerdoseratesallowforgreaterprobabilityofrepairprovidedthereissufficienttimeforthesingle-strandbreaktoberepairedpriortotheformationofadouble-strandbreakinthevicinitythus,twoneighboringsingle-strandbreaks(identicaltoadouble-strandbreak)lesslikelypossibilityofa“threshold”doserate本文檔共313頁；當(dāng)前第48頁；編輯于星期三\9點(diǎn)33分Radiation-InducedAberrations3majorlethalaberrationsdicentricringanaphasebridge2majornon-lethalaberrationstranslocationdeletion本文檔共313頁；當(dāng)前第49頁；編輯于星期三\9點(diǎn)33分Example:Dicentric雙著絲(lethal)Stepsintheformationofadicentricandanacentricfragment本文檔共313頁；當(dāng)前第50頁；編輯于星期三\9點(diǎn)33分Example:Ring(Lethal)Stepsintheformationofachromosomalring本文檔共313頁；當(dāng)前第51頁；編輯于星期三\9點(diǎn)33分Example:Bridge(Lethal)Stepsintheformationofananaphasebridgeandanacentricfragment本文檔共313頁；當(dāng)前第52頁；編輯于星期三\9點(diǎn)33分RearrangementsNotlethal;involvedincarcinogenesistranslocationbreaksintwochromosomesthestickyendsareexchangeddeletiontwobreaksinonechromosomeinformationbetweenthetwobreaksislost本文檔共313頁；當(dāng)前第53頁；編輯于星期三\9點(diǎn)33分SymmetricTranslocation(nonlethal)Pre-replicationchromosomesRadiationinducesbreaksinadjacentchromosomesBrokenpiecesexchangedNotnecessarilylethaltocellMayleadtocancerbecauseoflossofsuppressorgene(infragment)本文檔共313頁；當(dāng)前第54頁；編輯于星期三\9點(diǎn)33分SmallInterstitialDeletion(nonlethal)Pre-replicationchromosomesRadiationinducesadjacentbreaksinchromosomeFragmentlostatnextmitosisNotnecessarilylethaltocellMayleadtocancerbecauseoflossofsuppressorgene(infragment)Acentricring本文檔共313頁；當(dāng)前第55頁；編輯于星期三\9點(diǎn)33分ImplicationsPotentialforsomeaberrationstoleadtodisease,i.e.cancerSpecifictranslocationshavebeenassociatedwithseveralhumanmalignanciesNon-lethalaberrationscanbedetectedinirradiatedpersonsforupto40yearsafterexposurebiologicaldosimeters本文檔共313頁；當(dāng)前第56頁；編輯于星期三\9點(diǎn)33分ImplicationsTheformationofadicentric,ring,orbridgeusuallyleadstocelldeath“Cellsurvivalcurves”areusedtoquantifytheeffect本文檔共313頁；當(dāng)前第57頁；編輯于星期三\9點(diǎn)33分FrequencyofChromosomalAberrationsLinear-quadraticfunctionofdoseAberrationsresultfrom2separatebreaks本文檔共313頁；當(dāng)前第58頁；編輯于星期三\9點(diǎn)33分CellSurvivalCurveThecurveischaracterizedbytworegions:linearregion(aD)double-strandbreakfromasingleentitytheprobabilityofthissingleeventisproportionaltodose(D)quadraticregion(bD2)two,single-strandbreaksfromtwodifferententitiestheprobabilityofthesetwoeventsisproportionaltodose*dose(D2)本文檔共313頁；當(dāng)前第59頁；編輯于星期三\9點(diǎn)33分ReproductiveDeathCelldeathcanhavedifferentmeanings:lossofaspecificfunction-differentiatedcells(nerve,muscle,secretorycells)lossoftheabilitytodivideindefinitely–proliferatingcellssuchasstemcells干細(xì)胞inhematopoietic造血systemorintestinalepitheliumlossofreproductiveintegrity-“reproductivedeath”60本文檔共313頁；當(dāng)前第60頁；編輯于星期三\9點(diǎn)33分ReproductiveDeathConverse-“Survival”-retentionofreproductiveintegritythecapacityforsustainedproliferationincellsthatnormallyproliferate61本文檔共313頁；當(dāng)前第61頁；編輯于星期三\9點(diǎn)33分ReproductiveDeathMitoticDeathorApoptosisEndresultthesame–celllosesabilitytoproliferateindefinitely62本文檔共313頁；當(dāng)前第62頁；編輯于星期三\9點(diǎn)33分RelevantDose100Gydestroyscellfunctioninnon-proliferatingsystems(forexample:nerve,musclecells)2Gymeanlethaldoseforlossofproliferativecapacity63本文檔共313頁；當(dāng)前第63頁；編輯于星期三\9點(diǎn)33分SurvivalCurvesDescribesrelationshipbetweenradiationdoseandthefractionofcellsthat“survive”thatdoseUsedtoassessbiologicaleffectivenessfordifferentradiationtypesTheshapeofsurvivalcurvesaretell-tale64本文檔共313頁；當(dāng)前第64頁；編輯于星期三\9點(diǎn)33分SurvivalCurveShapeThesearethegeneralshapesofsurvivalcurvesformammaliancellsexposedtoradiationSemi-logplotsaretypicalMoredetaillater65本文檔共313頁；當(dāng)前第65頁；編輯于星期三\9點(diǎn)33分LinearEnergyTransfer(LET)傳能線密度LETistheaverageenergylocallyimparted(deposited)perunittracklength(keV/mm)Differentthan“stoppingpower”(energyloss)TrackaveragedvsenergyaveragedSometypicalvalues66本文檔共313頁；當(dāng)前第66頁；編輯于星期三\9點(diǎn)33分EnergyDepositionLow-LET(sparselyionizingradiation)x-raysgammabetas(higherenergy)High-LET(denselyionizingradiation)alphasbetas(lowerenergy)protonsneutrons67本文檔共313頁；當(dāng)前第67頁；編輯于星期三\9點(diǎn)33分LETofChargedParticlesEnergyLET68本文檔共313頁；當(dāng)前第68頁；編輯于星期三\9點(diǎn)33分PhotonEnergy-DepositionPathsClosestinshapeandstructuretothoseofbetasDistancebetweeninteractionsinoftenordersofmagnitudegreaterPhotonsaremuchmorepenetratingthanchargedparticles69本文檔共313頁；當(dāng)前第69頁；編輯于星期三\9點(diǎn)33分LETofPhotonsLETofphotonstendstoincreasewithenergyveryhighenergiesareanexception70本文檔共313頁；當(dāng)前第70頁；編輯于星期三\9點(diǎn)33分EnergyDepositionPathsforAlphasandBetasAlphapathsaregenerallystraightwithveryconcentratedenergydepositionBetapathsareveryrandom,energydepositioninteractionsaremoredispersed71本文檔共313頁；當(dāng)前第71頁；編輯于星期三\9點(diǎn)33分TypicalEnergyDepositionPathsforVariousRadiations72本文檔共313頁；當(dāng)前第72頁；編輯于星期三\9點(diǎn)33分73本文檔共313頁；當(dāng)前第73頁；編輯于星期三\9點(diǎn)33分SurvivalCurvesandLETIncreasingLET:increasestheslopeofthesurvivalcurveresultsinamorelinearcurveshoulderdisappearsduetoincreaseofkillingbysingle-events74本文檔共313頁；當(dāng)前第74頁；編輯于星期三\9點(diǎn)33分CharacteristicsofSurvivalCurvesLow-LETradiations:lowdoseregionsurvivalcurvebeginsaslinearonsemi-logplotsurvivingfractionisanexponentialfunctionofdosemiddoseregionshoulderregionappearshighdoseregionsurvivalcurvebecomeslinearagainandsurvivingfractionreturnstoanexponentialfunctionofdosesurvivingfractionisadualexponentialS=e-(aD+bD2)75本文檔共313頁；當(dāng)前第75頁；編輯于星期三\9點(diǎn)33分CharacteristicsofSurvivalCurvesHigh-LETradiations:survivalcurveislinearsurvivingfractionisapureexponentialfunctionofdoseS=e-(aD)76本文檔共313頁；當(dāng)前第76頁；編輯于星期三\9點(diǎn)33分SurvivalCurveExplanationSimpletoqualitativelydescribecurvesDifficultyliesinexplainingunderlyingbiophysicaleventsManymodelshavebeenproposedBiologicdatanotsufficientlyprecisetochooseamongthemodels77本文檔共313頁；當(dāng)前第77頁；編輯于星期三\9點(diǎn)33分TwoGeneralSurvivalModelsLinear-quadratic線性二次型model“dualradiationaction”firstcomponent-cellkillingisproportionaltodosesecondcomponent-cellkillingisproportionaltodosesquaredMulti-targetmodelbasedonprobabilityofhittingthe“target”widelyusedformanyyears;stillhasmerit78本文檔共313頁；當(dāng)前第78頁；編輯于星期三\9點(diǎn)33分LinearQuadraticModelS=e-(aD+bD2)where:SrepresentsthefractionofcellssurvivingDrepresentsdose

aandbareconstantsthatcharacterizetheslopesofthetwolinearportionsofthesemi-logsurvivalcurvebiologicalendpointiscelldeath79本文檔共313頁；當(dāng)前第79頁；編輯于星期三\9點(diǎn)33分LinearQuadraticModelLinearandquadraticcontributionstocellkillingareequalwhenthedoseisequaltotheratioofatobD=a/boraD=bD2

acomponentisrepresentativeofdamagecausedbyasingleevent(hit,double-strandbreak,“initiation/promotion”,etc.)

bcomponentisrepresentativeofdamagecausedbymultipleevents(hit/hit,2strandbreaks,initiationthenpromotion,etc.)80本文檔共313頁；當(dāng)前第80頁；編輯于星期三\9點(diǎn)33分aandbDetermination10010-110-2012369a/bbD2aDDose,GySurvival81本文檔共313頁；當(dāng)前第81頁；編輯于星期三\9點(diǎn)33分Multi-targetModelQuantifiedintermsof:measureofinitialslopeduetosingle-eventkilling,D1measureoffinalslopeduetomultiple-eventkilling,D0widthoftheshoulder,DqornD1andD0arereciprocalsoftheinitialandfinalslopesthedosesrequiredtoreducethefractionofsurvivingcellsby37%thedoserequiredtodeliver,onaverage,oneinactivatingeventpercell82本文檔共313頁；當(dāng)前第82頁；編輯于星期三\9點(diǎn)33分Why37%?S=exp[-aD],buthowdowedefinea?ifwedefineaastheslope,wherea=x/D0,thenxisthefractionalreductionofsurvivingcellsifallcellsareassumedtotakeonelethalhit,thenx=1anda=1/D0,sothatS=exp[-D/D0]=e-1=0.37Inradiationtherapy,itisusefultocalculatethemulti-fractioneddoserequiredtokill90%ofthepopulation(10%survival)0.1=exp[-D10/D0]D10=2.3D083本文檔共313頁；當(dāng)前第83頁；編輯于星期三\9點(diǎn)33分Multi-targetModelShoulder-widthmeasures:thequasi-thresholddose(Dq)thedoseatwhichtheextrapolatedlinefromthestraightportionofthesurvivalcurve(finalslope)crossesthedoseaxisat100%survivaltheextrapolationnumber(n)“broadshoulder”resultsinlargervalueofn“narrowshoulder”resultsinsmallvalueofnn=exp[Dq

/D0]84本文檔共313頁；當(dāng)前第84頁；編輯于星期三\9點(diǎn)33分Multi-TargetModelDose,Gy10010-110-4012369Survival10-310-2Initialslopemeasure,D1,duetosingle-eventkillingFinalslopemeasure,D0,duetomultiple-eventkillingDqnnorDqrepresentsthesizeorwidthoftheshoulder85本文檔共313頁；當(dāng)前第85頁；編輯于星期三\9點(diǎn)33分ModelParametersLinear-QuadraticModelMulti-TargetModel86本文檔共313頁；當(dāng)前第86頁；編輯于星期三\9點(diǎn)33分RelativeBiologicalEffectiveness

相對(duì)生物效應(yīng)Relatesbiologicaleffecttoa“standard”neededbecauseequalenergydepositionevents(doses)fromdifferentradiationsdonotproduceequaleffectsinbiologicalsystemsDefinition:RBEisdefinedastheratioofthestandarddosetothetestdoserequiredforequalbiologicaleffect2standards:250kVpxrays;60Cograysforexample:LD50for250kVpx-rays=6Gy(thestandard)LD50for2MeVneutrons=3Gy(thetestradiation)thus,theRBEfor2MeVneutronsis

287本文檔共313頁；當(dāng)前第87頁；編輯于星期三\9點(diǎn)33分RBEandFractionatedDosesWhathappenstotheRBEforneutronswhenthedoseisfractionated?endpoint=1%survival88本文檔共313頁；當(dāng)前第88頁；編輯于星期三\9點(diǎn)33分RBEandFractionatedDosesFractionatingthedoseincreasestheRBEforneutrons,notbecauseitincreasesthedamagedonebyneutrons,butbecauseitdecreasestheeffectofx-raysendpoint=1%survival89本文檔共313頁；當(dāng)前第89頁；編輯于星期三\9點(diǎn)33分RBEforDifferentCells/TissuesRBEalsovariesdependingontissuetypeandbiologicalendpointCellshavingaphotonsurvivalcurvewithalargeshoulder,indicatingthattheycanincurandrepairalargeamountofsublethalradiationdamage,showalargeRBEforneutronsCellshavingasmallshoulderintheirphotonsurvivalcurvehavesmallneutronRBEvaluesPhotonresponseimpactsneutronRBE90本文檔共313頁；當(dāng)前第90頁；編輯于星期三\9點(diǎn)33分VariabilityinRBERBEdependsonmanymorefactors:radiationqualitybiologicalendpointbiologicalsystemchoiceofradiation“standard”radiationdoseanddoseratenumberofdosefractions(&doseperfraction)91本文檔共313頁；當(dāng)前第91頁；編輯于星期三\9點(diǎn)33分HowisRBErelatedtoLET?AsLETincreases,thesurvivalcurveslopeincreasesandinitialshoulderdecreasesRBEincreaseswithLETuptoabout~100keV/mm92本文檔共313頁；當(dāng)前第92頁；編輯于星期三\9點(diǎn)33分TheOptimalLETAt~100keV/mm(~5MeVa)greatestRBE;producingmostbiologicaleffectperunitdoseseparationbetweenionizingevents~thediameterofDNAdoublehelixhighestprobabilityofdoublestrandbreakperunitdoseMoredenselyionizingradiationisjustaseffectivepertracklength,butlesseffectiveperunitdosesometimesreferredtoas“overkill”

93本文檔共313頁；當(dāng)前第93頁；編輯于星期三\9點(diǎn)33分CellSurvivalatVariousStagesofCellCycle-ChineseHamsterCellsDose(rad)6008001000120014000.00102004000.010.11.0Single-CellSurvival0.0005MESG2LSMx2.5(hypoxic)G194本文檔共313頁；當(dāng)前第94頁；編輯于星期三\9點(diǎn)33分SurvivingFractionofHeLaCells(3Gy)Time(hoursaftershake-off)101418220.10260.20.30.40.5Colony-SurvivingFraction0MS95本文檔共313頁；當(dāng)前第95頁；編輯于星期三\9點(diǎn)33分Radiosensitivity&MitoticCycleRadiosensitivity(generally)cellsaremostsensitiveclosetomitosisresistanceisgreatestinlatterpartofS-phaseforlongG1-phases,resistanceearlyfollowedbysensitivitylateG2andMequallysensitiveRepairislikelythekey96本文檔共313頁；當(dāng)前第96頁；編輯于星期三\9點(diǎn)33分MolecularCheckpointGenesCellularprogressionthroughcycleiscontrolledbycheckpointgenestoensurecompletionofeventspriortoprogressionatG2,cellsarehaltedtoinventory&repairdamagebeforemitosiscellswherecheckpointgeneisinactivated...…movedirectlytomitosis,evenwithdama