DNA Damage and Biological Expression of Adenovirus: A Comparison of Liquid versus Frozen Conditions of Exposure to γ Rays

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Abstract
Human adenovirus type 2 (Ad 2) was irradiated with 137Cs .gamma. rays in the liquid state at 0.degree. C. DNA breaks were correlated with the inactivation of several viral functions and compared to results obtained previously for irradiation of Ad 2 under frozen conditions at -75.degree. C. Irradiation at 0.degree. C induced 170 .+-. 20 single-strand breaks and 2.6 .+-. 0.4 double-strand breaks/Gy/1012 Da in the viral DNA. Viral adsorption to human KB cells was inactivated with a D0 of 9.72 .+-. 1.18 kGy, whereas the inactivation of Ad 2 plaque formation had a D0 of 0.99 .+-. 0.14 or 1.1 .+-. 0.29 kGy when corrected for the effect of radiation on virus adsorption. For the adsorbed virus, an average of 4.3 .+-. 1.7 single-strand and 0.065 .+-. 0.02 double-strand breaks were induced in the viral DNA per lethal hit. In contrast, irradiation of Ad 2 at -75.degree. C results in 2.6- to 3.4-fold less DNA breakage per Gy and a 5.6-fold increase in D0 for plaque formation of the adsorbed virus. Furthermore, although host cell reactivation (HCR) of Ad 2 viral structural antigen production for irradiated virus was substantially reduced in the xeroderma pigmentosum fibroblast strain (XP25RO) compared to normal strains for irradiation at -75.degree. C (57% HCR), it was only slightly reduced compared to normal for irradiation at 0.degree. C (88% HCR). These results indicate that the spectrum of DNA damage is both quantitatively and qualitatively different for the two conditions of irradiation.

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