2. Fifth Lecture

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

4. LIPID MEMBRANE OXIDATION HO. 2 or. OH + LH L. + H 2 O 2 or H 2 O L. + O 2 LOO. LOO. + L`H LOOH + L`. L`. + O 2 L`OO. L`OO. + L``H L`OOH + L``. Fe ++ + LOOH LO. + Fe +++ + OH - And so on

5. Effects of ionizing radiation on DNA &RNA 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. I S-AT-S I P I S-CG-S I P I S-GC-S I P I S-TA-S I

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.