Transcript Fifth Lecture

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.