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Transcript
Fifth Lecture DNA Protein Oxidative damage by free radicals Oxidized bases Strand breaks Crosslinkage Hydroxylation . OH Lipids OH R Phenylalanine R O-Tyrosine Peroxidation Alcohols Ketones Aldehydes Dialdehydes LIPID MEMBRANE OXIDATION . . HO 2 or OH + LH L . + O2 . LOO + L`H . L` + O2 . L`OO + L``H Fe++ + LOOH . L + H2O2 or H2O LOO . LOOH + L` L`OO . . L`OOH + L`` . And so on . LO + Fe+++ + OH - Effects of ionizing radiation on DNA &RNA I I S-AT-S I I P P I I S-CG-S I I P P I I S-GC-S I I P P 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. 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. 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. 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. 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. 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.