Chemical Investigations of the Molecular Origin of Biological Radiation Damage

Abstract

The radiation damage observed when U V and ionizing radiations react on biological objects is caused in many cases by changes in the nucleic acids. Exposure of these compounds to UV radiation in vitro and in vivo leads, inter alia, to dimerization of the pyrimidine bases with formation of cyclobutane derivatives, and to addition of water to the 5,6-double bond of the pyrimidine bases to form derivatives of the 6-hydroxyhydropyrimidine system. The structure of the irradiation products has been established. The dimerization prevents the reduplication of the DNA, and the addition of water appears to be the cause of UV mutations. Ionizing radiation in aqueous solution resulfs e.g. in addition of H and/ or HO radicals to the 5,6-double bond of the pyrimidine bases and cleavage of the imidazole ring af the purine bases. The mutations caused by ionizing radiation are probably also due, in part, to the formation of 6-hydroxydihydropyrimidine derivatives.

Ultraviolet Irradiation of Cytosine Nucleosides in Frozen Solution Produces Cyclobutane‐type Dimeric Products*

“…on biological systems are attributed to the photochemical transformation of pyrimidine bases in the nucleic acids [ 1,2]. While considerable progress has been made in understanding the nature of the products derived from uracil and thymine, much less is known about the photoproducts of cytosine and its derivatives [3,4]. The major products of cytidine and cytidylic acid irradiated with U.V.…”

“…Pyrimidine bases can conceivably give rise to four isomeric cyclobutanetype dimeric products[l5], and all four have been isolated for thymine [l6,17] and uracil [4]. With the available information it is not possible to establish the exact structural configuration of Cd,.…”

Experimental Modification of the Chemistry and Biology of the Aging Process

“…Not only ionizing but also UV radiation can catalyze transformations in the DNA structure (50). Photochemical attack takes place along the 5,6-double bond of pyrimidine bases, yielding water adducts (a) and cyclobutane-bridged dirners (h) as the UV radiation products (50).…”

“…Photochemical attack takes place along the 5,6-double bond of pyrimidine bases, yielding water adducts (a) and cyclobutane-bridged dirners (h) as the UV radiation products (50). In lower organisms, as well as in mammalian cells, direct and enzymatic photoreactivation restores the UV-damaged DNA (54).…”

The Role of Reactive Oxygen Species in the Light-Induced Deformation of DNA

“…1). The photoproducts (/-DNA) formed by a 2+2-cycloaddition (R eaction path b) [4] partly react back to D N A (R eaction path c). In princi ple the excited state can react directly with water (Reaction path d) [5] or else intract with oxygen in an electron or energy transfer reaction (Reaction path e ), which could contribute to the form ation of the oxygen species ('0 2 , 'O H , O O H , 0 3, 0 2~, H 20 2).…”