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Fifth Lecture

Fifth Lecture. Hydroxylation. Strand breaks. Oxidized bases. Cross- linkage. . OH. Phenylalanine. O-Tyrosine. Peroxidation. OH. R. R. Ketones. Dialdehydes. Alcohols. Aldehydes. DNA. Protein. Oxidative damage by free radicals. Lipids. LIPID MEMBRANE OXIDATION.

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Fifth Lecture

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  1. Fifth Lecture

  2. Hydroxylation Strand breaks Oxidized bases Cross- linkage .OH Phenylalanine O-Tyrosine Peroxidation OH R R Ketones Dialdehydes Alcohols Aldehydes DNA Protein Oxidative damage by free radicals Lipids

  3. LIPID MEMBRANE OXIDATION HO.2 or .OH + LH L. + H2O2 or H2O L. + O2 LOO. LOO. + L`H LOOH + L`. L`. + O2 L`OO. L`OO. + L``H L`OOH + L``. Fe+++ LOOH LO. + Fe+++ + OH- And so on

  4. Effects of ionizing radiation on DNA &RNA I I S-AT-S I I PP I I S-CG-S I I P P I I S-GC-S I I PP I I S-TA-S I I • DNA is the most important material making up the chromosomes. • It determines what types of RNA are produced which, in turn, determine the types of protein that are produced. • The DNA molecule takes the form of a twisted ladder or double helix. • The sides of the ladder are strands of alternating sugar and phosphate groups. Branching off from each sugar group is one of four nitrogenous bases: cytosine, thymine, adenine and guanine.

  5. Effects of ionizing radiation on DNA &RNA • DNA is the primary target for cell damage from ionizing radiation. • Toxic effects at low to moderate doses (cell killing, mutagenesis, and malignant transformation) appear to result from damage to cellular DNA. • Thus, ionizing radiation is a classical genotoxic agent.

  6. Effects of ionizing radiation on DNA &RNA Radiation can induce a variety of DNA lesions including:- • specific base damage, • Single strand breaks, • double strand breaks • and cross-linkage formation.

  7. Effects of ionizing radiation on DNA &RNA • Active enzymatic repair processes exist for the repair of both DNA base damage and strand breaks. • In many cases breaks in the double-strand DNA can be repaired by the enzymes, DNA polymerase, and DNA ligase. • The repair of double strand breaks involves recombinational events, depending upon the nature of the initial break.

  8. Radiation Induced Chromosome Damage • Chromosomes are composed of DNA, a macromolecule containing genetic information. • This large, tightly coiled, double stranded molecule is sensitive to radiation damage. • Radiation effects range from complete breaks of the nucleotide chains of DNA, to point mutations which are essentially radiation-induced chemical changes in the nucleotides.

  9. Radiation effects on Chromosomes • After irradiation, chromosomes may appear to be "sticky" with formation of temporary or permanent interchromosomal bridges preventing normal chromosome separation during mitosis and transcription of genetic information. • In addition, radiation can cause structural aberrations with pieces of the chromosomes break and form aberrant shapes. • Unequal division of nuclear chromatin material between daughter cells may result in production of nonviable, abnormal nuclei.

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