ON THE MECHANISM OF RADIOSENSITIZATION BY 5‐BROMOURACIL. THE OCCURRENCE OF DNA STRAND BREAKS IN U.V.‐IRRADIATED PHAGE T4 AS INFLUENCED BY CYSTEAMINE

Abstract

On the Mechanism of Radiosensitization by 5-Bromouradl.The Occ u r r enc e of DNA Strand Breaks in UV -Irradiated Phage T4 as Influenced by Cysteamine G. Hotz , R. Walser Photochemistry and Photobiology. 1970. Vol.12, pp. 207-218 Abstract-U.V.-irradiation of phage T4Bo" resuits in a decrease in sedimentation rate of BU-DNA which is attributed to single-and double-strand breaks. No breaks could be observed in unsubstituted DNA. Cysteamine present during u.v.-irradiation is able to prevent doublestrand breaks but does not influence the production of single-strand breaks rneasured by alkaline sucrose gradient centrifugation. The biological importance and nature of DNA strand breaks due to BU-incorporation as weIl as the action of the protective agent on these breaks and on the biological activity are discussed.

The Photolability of Dna Containing 5‐bromouracil‐i. Single‐strand Breaks and Alkali‐labile Bonds*

“…The calculated D, of 2.8 J/m2 for alkali-labile damage correlates closely with the Do of 3.5 J/m' for UV-inactivation of BrUra-).-phage titered on uurA host cells (Hewitt and Marburger, in preparation). Thus, conclusions drawn from carlier investigations that the breakage of BrUra-DNA measured in alkaline medium represents biologically significant photochemical damage to transforming DNA (Hutchinson and Hales, 1970) and bacteriophage (Hotz and Walser, 1970;Lion, 1970aLion, . 1970b) are supported by our studies.…”

“…Under appropriate conditions subsequent reactions can occur between the uracilyl radical and deoxyribose in the phosphodiester DNA backbone (Hotz and Reuschl, 1967; Kohnlein and Hutchirison. 1969) which yields breaks in the BrUra-containing strand (Lion, 1966;Hewitt et al, 1969;Hotz and Walser, 1970;Hutchinson and Hales, 1970;Lion, 1970a;Dodson et al, 1972). Less frequently, secondary reactions occur involving the complementary thymine or BrUra-containing strand (Kohnlein and Monkehaus, 1972;Beattie, 1972).…”

The Lesions Produced by Ultraviolet Light in DNA Containing 5-Bromouracil

“…When BrU-DNA is irradiated with ultraviolet light and then the strands separated by denaturation with alkali (Lion, 1968;Hewitt, Marburger & Lapthisophon, 1969;Hotz & Walser, 1970;Hutchinson & Hales, 1970) or formamide (Hutchinson & Hales, 1970;M. B.…”

“…Secondly, some cross-sections for single-strand breaks, when the DNA is irradiated in cells for example, are lower. It has been established that the destruction of sugar (Hotz & Reuschl, 1967), the number of single-strand breaks (Lion, 1968;Hotz & Walser, 1970;Stephan et al 1970) and the number of 5' ends (Dodson et al 1972) are reduced by the presence of sulphydryl compounds during irradiation. In terms of the model for the single-strand break developed in this review, the sulphydryl compounds would be viewed as donating H atoms either to the uracilyl radical or to the free radical in the sugar, preventing the break.…”

Oligonucleotide Photoproducts Formed by Photolysis of Polyribobromouridylic Acid

“…Altered bases have been found in irradiated BrU-DNA [2-41. There is evidence that at least part of the U.V. sensitization found upon incorporation of BrU into DNA is due to sugar damage [5,6] and backbone cleavage [7,8].…”