Oxidation of guanine in cellular DNA by solar UV radiation: biological role.
The formation of cyclobutane pyrimidine dimers (CPD) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) was investigated in Chinese hamster ovary cells upon exposure to either UVC, UVB, UVA or simulated sunlight (SSL). Two cell lines were used, namely AT3-2 and UVL9, the latter being deficient in nucleotide excision repair and consequently UV sensitive. For all types of radiation, including UVA, CPD were found to be the predominant lesions quantitatively. At the biologically relevant doses used, UVC, UVB and SSL irradiation yielded 8-oxodGuo at a rather low level, whereas UVA radiation produced relatively higher amounts. The formation of CPD was 10(2) and 10(5) more effective upon UVC than UVB and UVA exposure. These yields of formation followed DNA absorption, even in the UVA range. The calculated relative spectral effectiveness in the production of the two lesions showed that efficient induction of 8-oxodGuo upon UVA irradiation was shifted toward longer wavelengths, in comparison with those for CPD formation, in agreement with a photosensitization mechanism. In addition, after exposure to SSL, about 19% and 20% of 8-oxodGuo were produced between 290-320 nm and 320-340 nm, respectively, whereas CPD were essentially (90%) induced in the UVB region. However, the ratio of CPD to 8-oxodGuo greatly differed from one source of light to the other: it was over 100 for UVB but only a few units for UVA source. The extent of 8-oxodGuo and CPD was also compared to the lethality for the different types of radiation. The involvement of 8-oxodGuo in cell killing by solar UV radiation was clearly ruled out. In addition, our previously reported mutation spectra demonstrated that the contribution of 8-oxodGuo in the overall solar UV mutagenic process is very minor.
Douki
T
T
Département de Recherche Fondamentale sur la Matière Condensée, CEA/Grenoble, France.
Perdiz
D
D
Gróf
P
P
Kuluncsics
Z
Z
Moustacchi
E
E
Cadet
J
J
Sage
E
E
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects*; D004249:DNA Damage; D006147:Guanine / Q000737:chemistry / Q000528:radiation effects*; D009154:Mutation; D010084:Oxidation-Reduction; D018462:Photobiology; D011740:Pyrimidine Dimers / Q000737:chemistry / Q000528:radiation effects; D013472:Sunlight / Q000009:adverse effects
D011740:Pyrimidine Dimers; D006147:Guanine; D004247:DNA