erythemogenic than PM UV exposure –a contradiction to the
hypothesis that humans would display the opposite pattern
given that mice are nocturnal and humans are diurnal.10
Our study showed that the more erythemogenic AM exposure
also correlated with increased XPA in skin irradiated in the AM
versus the skin irradiated in the PM. This confirms the previous
findings that XPA in humans peaks at 07:00 h.27 XPA is 1 of 6
core factors in the human NER system10,28 and is responsible for
the rate-limiting step of excision.27 It is essential for the formation
of the pre-incision complex29 and recognizing DNA damage.27
XPA is regulated by the circadian clock as well as DNA damage.
Upon DNA damage, XPA is transported to the nucleus.30 Our
findings of increased XPA localization in the nucleus in the more
erythemogenic AM irradiated samples can be explained by both
the increased UV-induced DNA damage in the AM leading to increased
nuclear localization of XPA, as well as the effects of the
circadian clock elevating XPA in the AM. The relationship between
the elevated AM XPA and the increased erythema after AM UV
irradiation seems to contradict the relationship observed in mice.
In liver, brain, and skin from mice, XPA was found to increase during
the day and decrease during the night, peaking between 16:00
and 18:00 and dipping to the minimum between 04:00 and 06:00.27
Combining the results of our study and the mouse study, it seems
that the relationship between the circadian clock regulation of XPA
expression and the circadian clock regulation of erythema is confounded
by other factors that need to be elucidated.
Since erythema is the outcome of interest in most experimental testing
of photoprotective agents, this observed variation in AM versus
PM susceptibility to UV exposure may be an indication to improve
product testing protocols to account for this variability. This is similar
to the methods of other specialties, timing the delivery of therapies
to maximize efficacy based on known circadian cellular responses.
