Biological Effects of Ionizing Radiation Biological Effects of Ionizing Radiation Effects of Radiation Effects of Radiation

at the Molecular and Cellular Levelat the Molecular and Cellular Level

Effects of Radiation on CellsEffects of Radiation on CellsLectureLecture

IAEA Post Graduate Educational Course Radiation Protection and Safe Use of Radiation Sources

IAEA Post Graduate Educational Course in Radiation Protection and Safety of Radiation Sources

Module III.1 - Effects of Radiation at the Mollecula and the Cellular Level

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IntroductionIntroduction

This lecture presents information about This lecture presents information about structure of DNA, and mechanism of DNA structure of DNA, and mechanism of DNA damage by ionising radiationdamage by ionising radiation

It covers the topics describing DNA and It covers the topics describing DNA and chromosomal structure, stages of DNA chromosomal structure, stages of DNA metabolic process, damage to DNA by metabolic process, damage to DNA by ionising radiation, major types and ionising radiation, major types and mechanism of the damage, DNA repair mechanism of the damage, DNA repair process and mechanism process and mechanism

Module III.1 - Effects of Radiation at the Mollecula and the Cellular Level

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ContentContent

Chromosomal structure Chromosomal structure DNA structureDNA structure DNA metabolic processDNA metabolic process Damage to DNA by ionising radiation Damage to DNA by ionising radiation

(major types and mechanism)(major types and mechanism) DNA repair process and mechanismDNA repair process and mechanism DNA repair and human disordersDNA repair and human disorders

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OverviewOverview

Cell- as a principal target to ionising Cell- as a principal target to ionising radiationradiation

Effects of radiation on Cells:Effects of radiation on Cells: Effects on DNAEffects on DNA Chromosomal aberrationsChromosomal aberrations Cell inactivation or cell killingCell inactivation or cell killing Cell transformationCell transformation Cell mutationCell mutation

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Properties of genetic materialProperties of genetic material

Genetic material must be able to:Genetic material must be able to:

Be replicatedBe replicated Control expression of traits or Control expression of traits or

phenotypesphenotypes Change or to mutate in a controlled wayChange or to mutate in a controlled way

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Chromosomes as a deposit of Chromosomes as a deposit of hereditary materialhereditary material

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Histones Histones

Histones that form nucleosomes Histones that form nucleosomes (H2A, H2B, H3 et H4) - highly (H2A, H2B, H3 et H4) - highly positively-charged proteinspositively-charged proteins able to bind to DNA and one another, in able to bind to DNA and one another, in

the form of a nucleosomesthe form of a nucleosomes H1 histoneH1 histone

responsible for linking the nucleosomes responsible for linking the nucleosomes within the 30 nm chromatin fiberwithin the 30 nm chromatin fiber

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NucleosomeNucleosome

Nucleosome

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DNA structureDNA structure

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RNARNA

Is a single stranded DNA Is a single stranded DNA Is produced in the nucleus by Is produced in the nucleus by

transcription from opened DNA transcription from opened DNA moleculemolecule

Involved in the translationInvolved in the translation Types of RNA:Types of RNA:

MessengerMessenger TransferTransfer RibosomalRibosomal

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DNA metabolic processDNA metabolic process

CondensationCondensation Replication Replication TranscriptionTranscription RecombinationRecombination RepairRepair

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DNA replicationDNA replication

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Mechanism of DNA replicationMechanism of DNA replication

Mother cell DNA as a modelMother cell DNA as a model Necessity of complementary to the Necessity of complementary to the

original strandoriginal strand Each DNA nucleotide must be Each DNA nucleotide must be

recognizable by a non-polymerized recognizable by a non-polymerized nucleotidenucleotide

Two chains of the helix must be separated Two chains of the helix must be separated so that the groups of hydrogen-bond so that the groups of hydrogen-bond donors and acceptors are accessible for donors and acceptors are accessible for pairingpairing

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Enzymes involved in DNA Enzymes involved in DNA replicationreplication

TopoisomeraseTopoisomerase HelicaseHelicase DNA polymerase IIIDNA polymerase III PrimasePrimase LigaseLigase Single-stranded DNA binding Single-stranded DNA binding

proteinsproteins

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DNA transcription DNA transcription

Transcription is analogous to DNA Transcription is analogous to DNA replication. replication.

Difference from replication:Difference from replication: RNA is synthesized with DNA as template, andRNA is synthesized with DNA as template, and different enzymes are involveddifferent enzymes are involved

Stages:Stages: Initiation of transcriptionInitiation of transcription Termination of transcriptionTermination of transcription

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Transcription of DNA to Transcription of DNA to messenger RNAmessenger RNA

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DNA translationDNA translation

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Damage to DNA by ionising Damage to DNA by ionising radiationradiation

Major types of damage:Major types of damage:

base damage, base damage, single strand breaks, and single strand breaks, and double stand breakdouble stand break

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DNA base damageDNA base damage

The most common effect of radiation The most common effect of radiation on DNAon DNA

Easily repairedEasily repaired But may be severe enough to lead to But may be severe enough to lead to

cell deathcell death Often meant by the term mutation or Often meant by the term mutation or

genetic mutationgenetic mutation

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Single strand breaksSingle strand breaks Break or nick of the desoxyribose-base bond or Break or nick of the desoxyribose-base bond or

the phosphate-deoxyribose bond in a single the phosphate-deoxyribose bond in a single strand of DNAstrand of DNA

Result in a partial separation of the affected Result in a partial separation of the affected strand, over several nucleotidesstrand, over several nucleotides

Requires approximately 10-20 eV per breakRequires approximately 10-20 eV per break

Single strand breaks

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Separate degradation of both strands of DNA, for Separate degradation of both strands of DNA, for

a distance not farther than several nucleotidesa distance not farther than several nucleotides Can be produced by the same event or by two Can be produced by the same event or by two

separate eventsseparate events If unrepaired, result in broken chromosomesIf unrepaired, result in broken chromosomes

Double strand breaksDouble strand breaks

Double strand breaks

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DNA repair processDNA repair process

Mechanism of synthesis of repair Mechanism of synthesis of repair enzymesenzymes

Repair rate influence cell survivalRepair rate influence cell survival

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Mechanism of DNA repairMechanism of DNA repair

ExcisionExcision Recognition and elimination of the Recognition and elimination of the

damaged part of a DNA strand damaged part of a DNA strand

ResynthesisResynthesis reconstructing the original information reconstructing the original information

from the undamaged strandfrom the undamaged strand

Complete reconstructionComplete reconstruction

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DNA repair and human disordersDNA repair and human disorders

Xeroderma pigmentosum Xeroderma pigmentosum Fanconi’s anemiaFanconi’s anemia Ataxia teleangiectasiaAtaxia teleangiectasia

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SummarySummary

This lecture presented materials This lecture presented materials about structure of DNA, and about structure of DNA, and mechanism of DNA damage by mechanism of DNA damage by ionising radiationionising radiation

The materials of the lecture should The materials of the lecture should be learned at the introductory stage be learned at the introductory stage of radiobiology learning of radiobiology learning

Comments are welcomed Comments are welcomed

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Where to Get More InformationWhere to Get More Information Cell and Molecular Biology, E.D.P. De Robertis V., Cell and Molecular Biology, E.D.P. De Robertis V.,

De Robertis E.M.F., Info-Med Ltd; Hong Kong De Robertis E.M.F., Info-Med Ltd; Hong Kong (1998).(1998).

Physical and chemical mechanisms in molecular Physical and chemical mechanisms in molecular radiation biology. Glass W.A. and Varma M.N. Eds, radiation biology. Glass W.A. and Varma M.N. Eds, Plenum Press, New York 1991.Plenum Press, New York 1991.

Kiefer J. Biological Radiation effects. Springer Kiefer J. Biological Radiation effects. Springer Verlag, Berlin, Heidelberg 1990; 444.Verlag, Berlin, Heidelberg 1990; 444.

IAEA Regional Basic Professional Training Course IAEA Regional Basic Professional Training Course on Radiation Protection, Germany, 1997. Training on Radiation Protection, Germany, 1997. Training Materials. Materials.

IAEA Regional Basic Professional TrainingIAEA Regional Basic Professional Training Course Course on Radiation Protection, India, 1998. Training on Radiation Protection, India, 1998. Training MaterialsMaterials