一項(xiàng)研究發(fā)現(xiàn),，紫外線暴露的時(shí)間可能影響小鼠皮膚癌的出現(xiàn),。
暴露在紫外線輻射中能引發(fā)可能導(dǎo)致皮膚癌的DNA損傷,。此前對小鼠的研究已經(jīng)顯示了一種稱為XPA的蛋白質(zhì)—它參與了紫外線引發(fā)的DNA損傷的修復(fù)—的水平在一天中漲落,，在下午4—6點(diǎn)達(dá)到峰值,，在上午4—6點(diǎn)達(dá)到低谷,，這與生物鐘的節(jié)律一致,。
Aziz Sancar及其同事發(fā)現(xiàn)，在小鼠的皮膚細(xì)胞中,，這種蛋白質(zhì)的水平和活性在上午4點(diǎn)最低,，在下午4點(diǎn)最高。這組作者讓兩組小鼠暴露在紫外線輻射下——一組在上午4點(diǎn),，另一組在下午4點(diǎn)——并且監(jiān)測皮膚癌的出現(xiàn),。
在修復(fù)活動(dòng)處于最低點(diǎn)的時(shí)候接受輻射的小鼠比在這種蛋白質(zhì)的修復(fù)功能最強(qiáng)的時(shí)候接受輻射的小鼠出現(xiàn)腫瘤的速度遠(yuǎn)遠(yuǎn)更快，而且出現(xiàn)的頻率是后者的5倍,。當(dāng)這組作者在一種缺乏生物鐘的兩個(gè)關(guān)鍵成分的小鼠身上重復(fù)這一實(shí)驗(yàn)的時(shí)候,，紫外線暴露的時(shí)間沒有遵循這種蛋白質(zhì)的修復(fù)活動(dòng)或者皮膚癌的出現(xiàn)，這提示XPA蛋白質(zhì)的生物鐘控制可能影響皮膚癌的發(fā)病率,。這組作者說,，由于小鼠和人類的生物鐘類似，紫外線暴露的時(shí)間可能同樣地決定了它在人類身上的致癌潛力,。(生物谷 Bioon.com)
doi:10.1073/pnas.1115249108
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PMID:
Control of skin cancer by the circadian rhythm
Shobhan Gaddameedhi, Christopher P. Selby, William K. Kaufmann, Robert C. Smart, and Aziz Sancar
Skin cancer is the most common form of cancer in the United States. The main cause of this cancer is DNA damage induced by the UV component of sunlight. In humans and mice, UV damage is removed by the nucleotide excision repair system. Here, we report that a rate-limiting subunit of excision repair, the xeroderma pigmentosum group A (XPA) protein, and the excision repair rate exhibit daily rhythmicity in mouse skin, with a minimum in the morning and a maximum in the afternoon/evening. In parallel with the rhythmicity of repair rate, we find that mice exposed to UV radiation (UVR) at 4:00 AM display a decreased latency and about a fivefold increased multiplicity of skin cancer (invasive squamous cell carcinoma) than mice exposed to UVR at 4:00 PM. We conclude that time of day of exposure to UVR is a contributing factor to its carcinogenicity in mice, and possibly in humans.
