Cell cycle effects and concomitant p53 expression in hairless murine skin after longwave UVA (365 nm) irradiation: a comparison with UVB irradiation.
Ultraviolet A (UVA, 315-400 nm) radiation is known to be a complete carcinogen, but in contrast to UVB (280-315 nm) radiation, much of the cell damage is oxygen dependent (mediated through reactive oxygen species), and the dominant premutational DNA lesion(s) remains to be identified. To investigate further the basic differences in UVA and UVB carcinogenesis, we compared in vivo cellular responses, viz. cell cycle progression and transient p53 expression in the epidermis, after UVA1 (340-400 nm) exposure with those after broadband UVB exposure of hairless mice. Using flow cytometry we found a temporary suppression of bromodeoxyuridine (BrdU) uptake in S-phase cells both after UVB and UVA1 irradiation, which only in the case of UVB is followed by an increase to well over control levels. With equally erythemogenic doses (1-2 MED), the modulation of BrdU uptake was more profound after UVB than after UVA1 irradiation. Also, a marked transient increase in the percentage of S-phase cells occurred both after UVB and after UVA1 irradiation, but this increase evolved more rapidly after UVA1 irradiation. Further, p53 expression increased both after UVB and UVA1 irradiations, with peak expression already occurring from 12 to 24 h after UVA1 exposure and around 24 h after UVB exposure. Overall, UVA1 radiation appears to have less of an impact on the cell cycle than UVB radiation, as measured by the magnitude and duration of changes in DNA synthesis and cells in S phase. These differences are likely to reflect basic differences between UVB and UVA1 in genotoxicity and carcinogenic action.
de Laat
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Department of Dermatology, University Hospital Utrecht, Utrecht University, The Netherlands. J.M.T.DELAAT@DIGD.AZU.NL
Kroon
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de Gruijl
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D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D016158:Genes, p53; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays