Repair of pyrimidine(6-4)pyrimidone photoproducts in mouse skin.
The induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in the epidermal DNA of ultraviolet-irradiated hairless mice were determined by radioimmunoassay. Few cyclobutane dimers were excised by 48 h after ultraviolet (UV) irradiation, whereas 50% of the (6-4) photoproducts were removed by 6 h, correlating with previously determined rates of unscheduled DNA synthesis in mouse skin. After this initial rapid phase of (6-4) photoproduct excision, a slower phase was observed between 6 and 48 h. These repair kinetics contrast with those for fibroblast cell cultures derived from mouse tissues irradiated with UV light yielding similar levels of damage. Although the initial rate of (6-4) photoproduct repair in cultured fibroblasts and epidermal cells was similar, the extent of repair in cultured cells was significantly greater, with most of the damage removed by 24 h. The kinetics for (6-4) photoproduct repair in mouse epidermal cells suggest that a significant population, such as terminally differentiated keratinocytes, may have a reduced repair capacity and that the culture process may select for more rapidly proliferating, repair-proficient stem cells.
Mitchell
D L
DL
Laboratory of Radiobiology and Environmental Health, University of California, San Francisco 94143-0750.
Cleaver
J E
JE
Epstein
J H
JH
D000818:Animals; D002461:Cell Line, Transformed; D003503:Cyclobutanes; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D051379:Mice; D008812:Mice, Hairless; D011740:Pyrimidine Dimers / Q000235:genetics*; D011863:Radioimmunoassay; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D012879:Skin Physiological Phenomena; D014466:Ultraviolet Rays
D003503:Cyclobutanes; D011740:Pyrimidine Dimers; C058406:pyrimidine-pyrimidone dimer; D004247:DNA