Thursday, December 19, 2013

Radiation effect on DNA

DNA is double stranded large molecule with phosphoric acid, pentose sugar (2-deoxy-D-ribose) and organic bases. Phosphate moiety binds to the 5C of one end, the 3C of the neighbor pentose sugar to produce phosopho-diester linkage. The organic bases found in DNA are heterocyclic compounds containing nitrogen in their rings. So these are called nitrogenous bases. DNA normally contains adenine (A), guanine (G), thymine (T) and cytosine (C). Organic bases are linked with the pentose molecule to form nucleosides. This nucleoside binds with the phosphate group to form nucleotides.       

In DNA double helix number of pyrimidine bases is equal to that of purine bases. The two strands in a DNA are called complementary strands. The hydrogen bonds between A and T, and between C and G is known as complementary base pairing. There will be two hydrogen bonds between A and T, three hydrogen bonds between C and G. The chemical structure of DNA was shown in the figure1. DNA molecules are large molecules and packed into structures called chromosomes with the help of proteins (both histones and non-histones). Chromosomal aberrations may occur due to ionizing radiations. DNA is the primary target for cell damage from ionizing radiation compare to others which leads to mutations.

Mutations are sudden heritable changes. Agents which are responsible for inducing the mutations are called mutagens. Mutagens are of two types (physical mutagens and chemical mutagens). Physical mutagens are of types (non-ionizing and ionizing radiations). Alfa, beta and gamma radiations are ionizing radiations. They cause ionization of atoms in their path. So they are called ionizing radiations.
   
Alpha and beta radiations are particulate radiations, which consists of high energy atomic particles generated due to radioactive decay. Alpha rays are composed of alpha particles having two protons and neutrons devoid of electrons so they consist of double positive charge. Where as beta rays are high energy electrons produced by radioactive decay of 3H, 32P and 35S etc., and they are negatively charged. Gamma radiations are high energy radiations composed of photons. Gamma rays are non particulate rays. These are produced by decay of radioactive isotopes of 14C, 60C etc., Ionizing radiation remove the electron from its orbit around the nucleus of an atom.
   
Electron ejected from the atom A resulted in positive charge of the atom
Gamma rays produce ions in the above manner (Fig 2).  A high energy photon loses a part of its energy in removing electron from its orbit. The chemical effects of radiations are produced primarily due to ionization. The genetic effects of radiation result of their effects on DNA. The changes in DNA includes change in base (base substitution), loss of base (deletion and addition), disruption of hydrogen bond between nitrogen bases, single and double strand breaks and also cross linkage of proteins. Change in bases will produce missense, nonsense and frame-shift mutations. This will leads to gene mutations. Pyramidines are more sensitive to radiation when compare to purines.

The radiation damage to DNA occurs through two mechanisms (direct and indirect mechanisms). DNA damage caused by alpha, beta and gamma rays occurs when the displaced electron ionizes a water molecule, creating a free radical. As the free radical drifts, it may disrupt a DNA molecule. Direct damage is due to in which electron loss and electron gain within the DNA molecule which leads to instability of DNA molecule. Direct mechanism plays a more significant contribution to the DNA damage when compared to the indirect mechanism. Direct damage is predominant with alpha particles and indirect damage is predominant with gamma rays.             

Pospho di ester linkage break
The changes in the secondary structure of DNA caused by ionizing (gamma) radiations were studied by using circular dichroism and differential pulse polarography. Increase of the polarographic reducibility of DNA was observed on application of relatively low doses of radiation. Irradiation of DNA with low doses of gamma radiation induced local changes in angles and distances between the bases in the DNA double helix. Denatured DNA appeared after irradiating DNA with higher doses of ionizing radiation

Certain genes are responsible for rapid cell division which is called as oncogenes. Some other genes that slow down cell division and ultimately lead to cells death are called tumor suppressor genes. Cancers can be caused by DNA mutations (changes) that induce oncogenes or suppress tumor suppressor genes. First radiation-induced skin cancer reported in 1902. In 1920 bone cancer was observed among radium painters and in 1930 liver cancer was identified in Throtrast administration. However most DNA mutations related to breast cancer.

No comments:

Post a Comment