第七章射線的生物學(xué)效應(yīng)等演示文稿目前一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)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、滅菌目前二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)CellsFourconcepts(collectivelyknownascelltheory):thecellisthebasicstructuralandfunctionalunitoflivingorganisms-definingcellpropertiesdefineslifetheactivityofanorganismisdependentonboththeindividualandcollectiveactivitiesofitscellsaccordingtotheprincipleofcomplementarity,thebiochemicalactivitiesofcellsaredeterminedandmadepossiblebyspecificsubcellularstructurescontinuityoflifehasacellularbasisThehumanbodyhas~50-60trillioncells目前三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)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目前四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)IdealizedSchematicofaCellTwomajorsections:cytoplasmandnucleus目前五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)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)示意圖目前六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)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)目前七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)TheCellNucleusLargestorganelle(~5mmdia.)thickermembraneandmoreviscousfluidContainsthenucleolus核仁andchromatin染色質(zhì)

Gene-containingcontrolcenterthecellbrainregulatescellularprocessesMostcellscontainonenucleus,however,someareanucleate(nonucleus)-redbloodcellscannotreproduce;dieafterafewmonthsmulti-nucleate(severalnuclei)-skeletalmusclecells目前八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Chromosomes染色體Genes（基因）Chromatin（染色質(zhì)）DNALife’sBuildingBlocks目前九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DNADNA(deoxyribonucleicacid脫氧核糖核酸)isacoileddouble-helicalpolymer（聚合體）(strandsofproteinsandsugars)ThebaseunitofDNAiscalledthenucleotide（核苷酸）composedofadeoxyribose-sugarmoleculeslinkedtoaphosphategroup(adenine,guanine,cytosine,thymine)目前十頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DNAandChromatinSolenoidNucleosomeDNAH1CoreParticlechromatiniscomposedofnearlyequalamountsofDNAandglobular（球狀）histone（組蛋白）proteinshistonesprovideaphysicalmeansofpackagingtheDNAmoleculeinaverycompactandorderlyway;playsimportantroleingeneregulation目前十一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)LevelsofDNAcondensationDNAdouble-strandhelix.Chromatinstrand(DNAwithhistones).Condensedchromatinduringinterphase（間期）withcentromere（著絲點(diǎn)）.Condensedchromatinduringprophase.(TwocopiesoftheDNAmoleculearenowpresent)Chromosomeduringmetaphase.目前十二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ChromosomedetailsItisdifficulttoappreciatedetailsofchromosomestructureevenwithanelectronmicroscope.However,onelabelthemwithdyesthatarepreferentiallytakenupbycertainregionsThesemodificationscreateabandingpatternthatcanbeusedtoidentifyandcharacterizeindividualchromosomes.目前十三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DNAandChromosomesTounderstandhowtheDNAandhistonesareorganizedinachromosome,wemustappreciatethefactthatthenucleusisonly6micrometersindiameter.ThetotallengthofDNAinthehumangenomeis1.8meters.Thus,inordertopacktheDNAintothenucleusasinthephotographofthemetaphasechromosome,theremustbeseverallevelsofcoilingandsupercoiling.Thereisnearlya10,000-foldreductioninlengthinaninterphasenucleus.Eachchromosomecontains1longmoleculeofDNAplusassociatedhistones(basicproteins)whichhelpinthecondensationandregulationprocesses.目前十四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ChromosomeOrganizationDifferentlevelsofuncoilinginthechromosomeareshown.4nmDNAfilamentsarelabeledthe"DNAhelix".DoublestrandedDNAiswrappedaroundsetsof8histonestoforma10nmfilament.Setsof8histoneswrappedbyDNAareseparatedbyspacerregionsof4nmDNAfilament(doublestrandedDNA)andHistoneH1.arecalled"nucleosomes".Nnextlevelofcoilingproduces30nmnucleoproteinfibersFurtherloopingofnucleoproteinfibersaroundaproteinscaffoldformstheindividualmetaphasechromosomes目前十五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)GenesTheunitofgeneticmaterialresponsiblefordirectingcytoplasmicactivityandtransmittinghereditaryinformationEachgenecontainsafinitesectionofDNAwithspecificbasesequencecodingEachgenesoccupiesaspecificchromosomallocus目前十六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ChromosomesEachchromosomecontainsmanygenesarrangedinaspecificlinearsequenceConstrictedatcertainpointsbyacentromere,aclearregionnecessaryformovementofthechromosomeduringcelldivisionChromosomesareconstantinnumberforeachspecies目前十七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)RelativeSizesofGeneticMaterials目前十八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)TheCellLifeCycleTheseriesofchangesacellgoesthroughfromthetimeitisformeduntilitreproducesisitslifecycleThelifecycleiscomprisedoftwomajorperiods:Interphase間期cellgrowsandcarriesonitsusualactivitiesMitosis有絲分裂(mitoticphase)cellularreproduction目前十九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)TheCellCycle目前二十頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)InterphaseThe“growthphase”;preparingfornextdivisionTotalperiodfromcellformationtocelldivisionDuringInterphasethechromosomalmaterialisseenintheformofdiffusechromatinInterphaseisdividedintoG1,S,andG2sub-phases:G1-(1stgrowthperiod)cellssynthesizeproteinsandgrowvigorouslyS-(synthesis)replicationofDNAG2-(2ndgrowthperiod)enzymes酶/proteinsneededfordivisionaresynthesizedandmovedtotheirpropersites目前二十一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DNAReplicationSphaseMustoccurbeforedivision,sothatidenticalcopiesofthecell’sgenescanbepassedonProcessincludes:anenzymeuncoils,untwistsandseparatestheDNAmoleculeintotwocomplementarynucleotide核苷酸chainstwoidenticalstrandsofDNAresulteachstrandhashalfoftheoldDNAmoleculeandhalfisnewlysynthesized目前二十二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)MitosisCelldivisionDividedintofourdistinctphases:prophase(earlyandlate)metaphaseanaphase

telophase(andcytokinesis)目前二十三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)TheCommonTheoryofBiologicalDamageResultingfromRadiationExposure目前二十四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Review-EnergyLossbychargedparticlesHeavychargedparticleslosekineticenergyviaasequenceofsmallenergytransferstoatomicelectronsinthemedium.Mostenergydepositionoccursintheinfratrack,anarrowregionaroundtheparticletrackextendingabout10atomicdistances.Ionizationoutsidetheinfratrackiscausedbyveryenergeticparticlesthatescapefromtheinfratrackandsecondaryelectrons.Themoreenergeticinteractionsejectelectronsfromtheirparentatomsandgenerateprimaryion-pairs.AnapproximateexpressionforthemaximumenergytransfertoanelectronfromaheavychargedparticleofmassnumberAandenergyE(MeV)isgivenby:Wmax=215E/AwhereWmaxisineV.Thussecondaryelectronsgeneratedbya5MeValphaparticlerangeuptoabout300eVofkineticenergy.目前二十五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)EnergyLossbychargedparticlesEnergeticsecondarye’scaninitiateadditionalionizations,whilelessenergeticonesinduceelectronicexcitations.Lowestenergysecondarye’sarereferredtoas"sub-excitation",whoseroleinbiologicalradiationdamageremainsunclear.Onlyasmallfractionofinitialenergyistransferredateachevent,atrackconsistingofclustersofionsorspursisgeneratedalongthepathofthemovingparticle.Mostspursinwatercomprise1-5ion-pairs.Thesetracksmaybevisualizedinacloudchamberbytheirvaportrail.High-energysecondaryelectronsareoccasionallygenerated.Energylossbytheseenergeticelectronsleadstoshortbranchingtracksor"deltarays"Deltaraysmayterminateinlargerpear-shapedregionsofionisationor"blobs".Similarconsiderationsapplyforenergytransfertoafluidmediuminindirectaction.目前二十六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)EnergyLossbychargedparticlesSpursandexcitationsinthetrackofanalpha-particleinwater.Eachcircledepictsanionizationorexcitationevent.Thebranchingtracksare"deltarays".100Angstrom目前二十七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DistributionofIon-pairsinwaterfrompassageoffastelectronsandbetaparticlesFastelectrons&betasloseenergybyinelasticcollisionswithelectronsofthemedium.Electronstracksarelessdensethanthetracksofheavychargedparticles,owingtothelowerLET,andthespursaremorewidelyspacedwithmorefrequentdeltaraysterminatingwithblobs.Onlyabout20%ofbetaparticlespenetratetothemaximumrangeowingtotheirbroadenergydistribution.Inadditiontoenergydeposition,electronsundergoelasticelectron-electroncollisionsleadingtomultiplescatteringandcurvatureofthetrackswhichcomplicatethedosimetryinextendedsources目前二十八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Shorttracks>5000eV<5000eVPrimarypathSpurs100to500eVblobs<100eVDeltaRaysBranchtracksIonpaircreationinwaterfromSecondaryElectrons目前二十九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DirectandIndirectActionBiologicaleffectsofradiationresultprincipallyfromdamagetotheDNADNAisthe“criticaltarget”Targetcanreceivedirectdamagedbyphysicalinteractionwithradiation,orindirectdamagedbyfreeradicalsformedwhenradiationinteractswithwatermoleculesinthecell目前三十頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DirectActionPhysicalinteractionthatdirectlyionizestheDNAmoleculeDNAdamageresultsfromthephysicalbreakageofchemicalbondswithintheDNAbackboneNucleotidebonds,phosphatebondsorstrandbreaksmayresultfromradiationdamageThisdamagemayormaynotberepairable目前三十一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)IndirectActionH2O+hn-->H2O++e--->H?+?OHChemicalinteractionsH2O+isanion(charged)electronejectedfromthewatermolecule?OHisthehydroxyradicalafreeradicalhasanunpairedelectronfromabrokencovalentbondandisveryreactivemustbeincloseproximitytoDNAtodoitsdamagebychemicalreaction目前三十二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DirectandIndirectAction:

Neutrons目前三十三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DirectandIndirectAction:

PhotonsIndirectActionDominantforLowLETRadiation目前三十四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)EnergyAbsorptioninRadiobiologyEnergyisabsorbed,butdamageisdonebybreakingchemicalbondsEnergydepositedincellsandtissuesunevenlyindiscretepacketsaverageabsorptionperionizingevent~34eVtypicalC=Cbindingenergy4.9eVremaindergoesintootherionization,excitation,andbiologicaldamage目前三十五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)TimeScaleofEventsInitialionization:~10-15secFree-ionlifetime:~10-10secFree-radicallifetime:~10-5secBreakageofbondsandexpressionofbiologicaleffectscelldeath:hourstodaysoncogenesis:yearsgermcellmutation:generations目前三十六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ClassicParadigmofRadiationInjury←1s→←min-hrs→←days→←weeks→←months→←years→←generations→IonizingRadiationDNADamageCellDeathDNAMutationHeritableEffectsCancerDevelopmentaleffects(fetal)LateeffectsChemicalRepair(ionsrecombine)Ionizations(freeradicalformation,etc)ExcitationsHeatEnzymaticDNARepairEarly(Acute)Effects(Radiationsickness)目前三十七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DNAStrandBreaksDNAcansuffersingleanddoublestrandbreaksStrongcircumstantialevidencethatDNAisprincipaltargetforcellkillingAsingle-strandbreakoccurswhenonlyoneofthehelicessuffersabreakAdouble-strandbreakoccurswhenbothhelicessufferabreakeitherdirectlyoppositeoneanotherorwhenseparatedbyonlyafewbasepairs目前三十八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DiagramofsingleanddoublestrandDNAbreaksGGGGCCCCAAATTT2nmBlob7nmdiameter,12ionpairsSpur4nmdiameter,3ionpairs目前三十九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DiagramofsingleanddoublestrandDNAbreaksGGGGCCCCAAATTTSinglestrandbreak目前四十頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DiagramofsingleanddoublestrandDNAbreaksGGGGCCCCAAATTTWellseparateddoublestrandbreak目前四十一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)DiagramofsingleanddoublestrandDNAbreaksGGGCCCCAAATTTAdjacentdoublestrandbreakGGGGCCCAAATTT目前四十二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Single-StrandBreaksReadilyrepairedusuallydoesnotleadtomutationsorcelldeathImproperrepairispossiblenormallyleadstomutationsordeath目前四十三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Double-StrandBreaksDifficultorimpossibletorepairmayleadtoprogrammedcelldeath(apoptosis),mutationorcarcinogenesisIfnotrepaired,orrepairisinerror,mutationsmaybereplicatedmayleadtocellsthatfunctionimproperlyandhaveunregulatedcellgrowth(e.g.,cancer)目前四十四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)FragmentBehavior(post-break)RepairbreaksmayrejoinintheiroriginalconfigurationAberrationbreaksmayfailtorejoinbrokenendsmayrejoinotherbrokenends,etcoccursatnextmitosis目前四十五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ChromosomalAberrationsOftencausedbybreakageandincorrectrejoiningbrokensegmentsmayremainseparatedfromminutestohours;endsaresaidtobe“sticky”theyarecapableofreattachingtoanyotherbrokensegments(mostoftenrejoiningintheiroriginalconfiguration)breaksduringspecificphasesofmitosisresultindifferentendpoints(aswewillsee)目前四十六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Radiation-InducedAberrationsOccurwhencellisirradiatedbeforethechromosomematerialhasbeenduplicatedFrequencyofsingle-strandbreaksincreaseslinearlywithradiationdoseFrequencyofdouble-strandbreaksincreaseswithdoseasapowerfunction(powerof~1.5to2)目前四十七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Radiation-InducedAberrationsDose-rateeffectforsingle-strandbreakslowerdoseratesallowforgreaterprobabilityofrepairprovidedthereissufficienttimeforthesingle-strandbreaktoberepairedpriortotheformationofadouble-strandbreakinthevicinitythus,twoneighboringsingle-strandbreaks(identicaltoadouble-strandbreak)lesslikelypossibilityofa“threshold”doserate目前四十八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Radiation-InducedAberrations3majorlethalaberrationsdicentricringanaphasebridge2majornon-lethalaberrationstranslocationdeletion目前四十九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Example:Dicentric雙著絲(lethal)Stepsintheformationofadicentricandanacentricfragment目前五十頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Example:Ring(Lethal)Stepsintheformationofachromosomalring目前五十一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Example:Bridge(Lethal)Stepsintheformationofananaphasebridgeandanacentricfragment目前五十二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)RearrangementsNotlethal;involvedincarcinogenesistranslocationbreaksintwochromosomesthestickyendsareexchangeddeletiontwobreaksinonechromosomeinformationbetweenthetwobreaksislost目前五十三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)SymmetricTranslocation(nonlethal)Pre-replicationchromosomesRadiationinducesbreaksinadjacentchromosomesBrokenpiecesexchangedNotnecessarilylethaltocellMayleadtocancerbecauseoflossofsuppressorgene(infragment)目前五十四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)SmallInterstitialDeletion(nonlethal)Pre-replicationchromosomesRadiationinducesadjacentbreaksinchromosomeFragmentlostatnextmitosisNotnecessarilylethaltocellMayleadtocancerbecauseoflossofsuppressorgene(infragment)Acentricring目前五十五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ImplicationsPotentialforsomeaberrationstoleadtodisease,i.e.cancerSpecifictranslocationshavebeenassociatedwithseveralhumanmalignanciesNon-lethalaberrationscanbedetectedinirradiatedpersonsforupto40yearsafterexposurebiologicaldosimeters目前五十六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ImplicationsTheformationofadicentric,ring,orbridgeusuallyleadstocelldeath“Cellsurvivalcurves”areusedtoquantifytheeffect目前五十七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)FrequencyofChromosomalAberrationsLinear-quadraticfunctionofdoseAberrationsresultfrom2separatebreaks目前五十八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)CellSurvivalCurveThecurveischaracterizedbytworegions:linearregion(aD)double-strandbreakfromasingleentitytheprobabilityofthissingleeventisproportionaltodose(D)quadraticregion(bD2)two,single-strandbreaksfromtwodifferententitiestheprobabilityofthesetwoeventsisproportionaltodose*dose(D2)目前五十九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ReproductiveDeathCelldeathcanhavedifferentmeanings:lossofaspecificfunction-differentiatedcells(nerve,muscle,secretorycells)lossoftheabilitytodivideindefinitely–proliferatingcellssuchasstemcells干細(xì)胞inhematopoietic造血systemorintestinalepitheliumlossofreproductiveintegrity-“reproductivedeath”60目前六十頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ReproductiveDeathConverse-“Survival”-retentionofreproductiveintegritythecapacityforsustainedproliferationincellsthatnormallyproliferate61目前六十一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ReproductiveDeathMitoticDeathorApoptosisEndresultthesame–celllosesabilitytoproliferateindefinitely62目前六十二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)RelevantDose100Gydestroyscellfunctioninnon-proliferatingsystems(forexample:nerve,musclecells)2Gymeanlethaldoseforlossofproliferativecapacity63目前六十三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)SurvivalCurvesDescribesrelationshipbetweenradiationdoseandthefractionofcellsthat“survive”thatdoseUsedtoassessbiologicaleffectivenessfordifferentradiationtypesTheshapeofsurvivalcurvesaretell-tale64目前六十四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)SurvivalCurveShapeThesearethegeneralshapesofsurvivalcurvesformammaliancellsexposedtoradiationSemi-logplotsaretypicalMoredetaillater65目前六十五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)LinearEnergyTransfer(LET)傳能線密度LETistheaverageenergylocallyimparted(deposited)perunittracklength(keV/mm)Differentthan“stoppingpower”(energyloss)TrackaveragedvsenergyaveragedSometypicalvalues66目前六十六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)EnergyDepositionLow-LET(sparselyionizingradiation)x-raysgammabetas(higherenergy)High-LET(denselyionizingradiation)alphasbetas(lowerenergy)protonsneutrons67目前六十七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)LETofChargedParticlesEnergyLET68目前六十八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)PhotonEnergy-DepositionPathsClosestinshapeandstructuretothoseofbetasDistancebetweeninteractionsinoftenordersofmagnitudegreaterPhotonsaremuchmorepenetratingthanchargedparticles69目前六十九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)LETofPhotonsLETofphotonstendstoincreasewithenergyveryhighenergiesareanexception70目前七十頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)EnergyDepositionPathsforAlphasandBetasAlphapathsaregenerallystraightwithveryconcentratedenergydepositionBetapathsareveryrandom,energydepositioninteractionsaremoredispersed71目前七十一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)TypicalEnergyDepositionPathsforVariousRadiations72目前七十二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)73目前七十三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)SurvivalCurvesandLETIncreasingLET:increasestheslopeofthesurvivalcurveresultsinamorelinearcurveshoulderdisappearsduetoincreaseofkillingbysingle-events74目前七十四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)CharacteristicsofSurvivalCurvesLow-LETradiations:lowdoseregionsurvivalcurvebeginsaslinearonsemi-logplotsurvivingfractionisanexponentialfunctionofdosemiddoseregionshoulderregionappearshighdoseregionsurvivalcurvebecomeslinearagainandsurvivingfractionreturnstoanexponentialfunctionofdosesurvivingfractionisadualexponentialS=e-(aD+bD2)75目前七十五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)CharacteristicsofSurvivalCurvesHigh-LETradiations:survivalcurveislinearsurvivingfractionisapureexponentialfunctionofdoseS=e-(aD)76目前七十六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)SurvivalCurveExplanationSimpletoqualitativelydescribecurvesDifficultyliesinexplainingunderlyingbiophysicaleventsManymodelshavebeenproposedBiologicdatanotsufficientlyprecisetochooseamongthemodels77目前七十七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)TwoGeneralSurvivalModelsLinear-quadratic線性二次型model“dualradiationaction”firstcomponent-cellkillingisproportionaltodosesecondcomponent-cellkillingisproportionaltodosesquaredMulti-targetmodelbasedonprobabilityofhittingthe“target”widelyusedformanyyears;stillhasmerit78目前七十八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)LinearQuadraticModelS=e-(aD+bD2)where:SrepresentsthefractionofcellssurvivingDrepresentsdose

aandbareconstantsthatcharacterizetheslopesofthetwolinearportionsofthesemi-logsurvivalcurvebiologicalendpointiscelldeath79目前七十九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)LinearQuadraticModelLinearandquadraticcontributionstocellkillingareequalwhenthedoseisequaltotheratioofatobD=a/boraD=bD2

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

bcomponentisrepresentativeofdamagecausedbymultipleevents(hit/hit,2strandbreaks,initiationthenpromotion,etc.)80目前八十頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)aandbDetermination10010-110-2012369a/bbD2aDDose,GySurvival81目前八十一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Multi-targetModelQuantifiedintermsof:measureofinitialslopeduetosingle-eventkilling,D1measureoffinalslopeduetomultiple-eventkilling,D0widthoftheshoulder,DqornD1andD0arereciprocalsoftheinitialandfinalslopesthedosesrequiredtoreducethefractionofsurvivingcellsby37%thedoserequiredtodeliver,onaverage,oneinactivatingeventpercell82目前八十二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)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目前八十三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Multi-targetModelShoulder-widthmeasures:thequasi-thresholddose(Dq)thedoseatwhichtheextrapolatedlinefromthestraightportionofthesurvivalcurve(finalslope)crossesthedoseaxisat100%survivaltheextrapolationnumber(n)“broadshoulder”resultsinlargervalueofn“narrowshoulder”resultsinsmallvalueofnn=exp[Dq

/D0]84目前八十四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Multi-TargetModelDose,Gy10010-110-4012369Survival10-310-2Initialslopemeasure,D1,duetosingle-eventkillingFinalslopemeasure,D0,duetomultiple-eventkillingDqnnorDqrepresentsthesizeorwidthoftheshoulder85目前八十五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)ModelParametersLinear-QuadraticModelMulti-TargetModel86目前八十六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)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目前八十七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)RBEandFractionatedDosesWhathappenstotheRBEforneutronswhenthedoseisfractionated?endpoint=1%survival88目前八十八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)RBEandFractionatedDosesFractionatingthedoseincreasestheRBEforneutrons,notbecauseitincreasesthedamagedonebyneutrons,butbecauseitdecreasestheeffectofx-raysendpoint=1%survival89目前八十九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)RBEforDifferentCells/TissuesRBEalsovariesdependingontissuetypeandbiologicalendpointCellshavingaphotonsurvivalcurvewithalargeshoulder,indicatingthattheycanincurandrepairalargeamountofsublethalradiationdamage,showalargeRBEforneutronsCellshavingasmallshoulderintheirphotonsurvivalcurvehavesmallneutronRBEvaluesPhotonresponseimpactsneutronRBE90目前九十頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)VariabilityinRBERBEdependsonmanymorefactors:radiationqualitybiologicalendpointbiologicalsystemchoiceofradiation“standard”radiationdoseanddoseratenumberofdosefractions(&doseperfraction)91目前九十一頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)HowisRBErelatedtoLET?AsLETincreases,thesurvivalcurveslopeincreasesandinitialshoulderdecreasesRBEincreaseswithLETuptoabout~100keV/mm92目前九十二頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)TheOptimalLETAt~100keV/mm(~5MeVa)greatestRBE;producingmostbiologicaleffectperunitdoseseparationbetweenionizingevents~thediameterofDNAdoublehelixhighestprobabilityofdoublestrandbreakperunitdoseMoredenselyionizingradiationisjustaseffectivepertracklength,butlesseffectiveperunitdosesometimesreferredtoas“overkill”

93目前九十三頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)CellSurvivalatVariousStagesofCellCycle-ChineseHamsterCellsDose(rad)6008001000120014000.00102004000.010.11.0Single-CellSurvival0.0005MESG2LSMx2.5(hypoxic)G194目前九十四頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)SurvivingFractionofHeLaCells(3Gy)Time(hoursaftershake-off)101418220.10260.20.30.40.5Colony-SurvivingFraction0MS95目前九十五頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)Radiosensitivity&MitoticCycleRadiosensitivity(generally)cellsaremostsensitiveclosetomitosisresistanceisgreatestinlatterpartofS-phaseforlongG1-phases,resistanceearlyfollowedbysensitivitylateG2andMequallysensitiveRepairislikelythekey96目前九十六頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)MolecularCheckpointGenesCellularprogressionthroughcycleiscontrolledbycheckpointgenestoensurecompletionofeventspriortoprogressionatG2,cellsarehaltedtoinventory&repairdamagebeforemitosiscellswherecheckpointgeneisinactivated...…movedirectlytomitosis,evenwithdamagedchromosomes…aremoresensitivetoUVorionizingradiation(oranyDNAdamagingagent)97目前九十七頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)LifeCycle&CheckpointGenesG2MSG198目前九十八頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)EffectsofOxygenationOxygenenhancementratio(OER)aeratedcellsaremoreradiosensitive(dueto“fixing”)oxygenreactswithfreeradicalstoproduceperoxide,whichconstitutesnon-repairabledamagetypicalvalues:2.5-3forgandx-raysG1:~2.3S:~2.8G2:intermediate(~1.5)Providesimplicationsforradiationtherapymodes99目前九十九頁(yè)\總數(shù)三百一十三頁(yè)\編于十四點(diǎn)UtilizingCycleSensitivityin

TumorTherapyTumorcellsinitiallyasynchronousDosedeliveredMostsensitivecells(Mphase)killedPopulat