If you can't bear to face your inbox before your first cup of coffee, you'll sympathize with cells in your body that are better equipped to face some challenges at certain times of day. Carcinogens, such as ultraviolet radiation, may be one such challenge. Can we lower our cancer risk by limiting our carcinogen exposure to certain hours of the day?
Circadian rhythms are day-long cycles that ebb and flow like tides within our bodies. We use the sun to keep our internal clocks calibrated. But even if left in a dark room for days on end, our bodies maintain their rhythms. Our internal temperatures, levels of circulating hormones, and activity of various genes within our cells all rise and fall throughout the day.
One of the genes that follows a daily cycle is responsible for making a DNA-repair protein called XPA. When your DNA is damaged, a molecular task force within the cell identifies the bad spot, snips it out, and fills in the gap with fresh nucleotides. XPA is a crucial member of this task force. Researchers in North Carolina wanted to know how the cycling of XPA affects skin cancer. When XPA is off-duty--when its daily cycle reaches its lowest point--are skin cells more vulnerable to cancer-causing sun damage?
To find out, the researchers used hairless mice that are bred to develop humanlike skin cancer. Mice have an internal clock that's nearly identical to that of humans, and repair their DNA in the same way. The researchers exposed one group of mice to UV radiation at 4 AM, the lowest point of their XPA cycle. Another group of mice was exposed at 4 PM, the high point, instead.
For the 12 hours following UV exposure, the researchers monitored the rate of DNA repair in mouse skin cells. They saw that in the afternoon group, repair happened quickly, thanks to the high amounts of XPA at work. But in the morning-exposure group, DNA repair was delayed significantly.
Does this delay in fixing DNA errors add up to cancer? The researchers again divided the mice into groups. One group was exposed to UV radiation at 4 AM, three days a week, for 25 weeks. The second group was again exposed to UV at 4 PM, and a third group was left alone.
Both groups of mice exposed to UV developed skin tumors. But the group that got its UV radiation in the early morning grew tumors sooner. Those mice also had twice as many tumors as the afternoon UV group, and their tumors were nearly twice as wide. (All this evidence was easily, and disgustingly, visible due to their hairlessness.)
In humans, damage and repair likely follow the same rhythm. But there's one major difference: Since mice are nocturnal, their clock is opposite to ours. Hormones that are needed during waking hours, for instance, would peak during the night in mice and during the day in humans. In an earlier study, the researchers found that XPA follows a circadian rhythm in humans just as it does in mice--but for us, production is highest in the early morning.
Our levels of XPA peak around 7 AM. Based on this study, our ability to protect our skin from cancer-causing sun damage probably peaks at the same time. Adding to the danger is the fact that in both humans and mice, DNA replication follows a cycle opposite to XPA production. This means that when XPA is lowest, more DNA is being stitched together--making the risk of errors even higher.
The authors suggest that if we must expose ourselves to UV radiation, we do so in the morning. We should avoid the sun in afternoon and evening hours, when XPA is lowest and our skin cells are most vulnerable to carcinogenic damage. Of course, unless you live in the Arctic circle, you're not likely to get a lot of dangerous sun exposure at 7 PM. But for people who use tanning beds, sessions late in the day may be more harmful than those in the morning.
There may be other carcinogens whose danger varies throughout the day, depending on how hormones and other molecules are cycling through our affected organs. Is there an ideal time of day to smoke a cigarette? Eat a hot dog? Have an x-ray? If we can't remove risks from our lives, maybe we can at least reschedule them.
Gaddameedhi, S., Selby, C., Kaufmann, W., Smart, R., & Sancar, A. (2011). Control of skin cancer by the circadian rhythm Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1115249108
