Lu Yao-Ping, Lou You-Rong, Peng Qing-Yun, Xie Jian-Guo, Conney Allan H
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Cancer Res. 2004 Jul 15;64(14):5020-7. doi: 10.1158/0008-5472.CAN-04-0760.
Shaved male or female p53(-/-) C57BL/6J mice and their wild-type littermates were irradiated once with UVB (60 mJ/cm(2)). The UVB-induced increase in apoptotic sunburn cells in p53(-/-) mice at 6-10 h after exposure to UVB was only 10-30% of that observed after treatment of p53(+/+) mice with UVB. Topical applications of caffeine immediately after UVB irradiation in female p53(+/+) or p53(-/-) mice enhanced the UVB-induced increase in apoptotic sunburn cells 6 h later by 127% and 563%, respectively. In another study, shaved female Bax(-/-) C57BL/6J mice and their wild-type littermates were irradiated once with UVB (60 mJ/cm(2)). The UVB-induced increase in apoptotic sunburn cells in Bax(-/-) mice at 6 h after exposure to UVB was only 14% of that observed after treatment of Bax(+/+) mice with UVB. Topical application of caffeine immediately after irradiation of Bax(+/+) or Bax(-/-) mice with UVB enhanced the UVB-induced increases in apoptotic sunburn cells at 6 h by 214% and 467%, respectively, and topical application of caffeine immediately after irradiation of Bax(+/+) or Bax(-/-) mice with UVB enhanced the UVB-induced increase in caspase 3 (active form) positive cells at 6 h by 253% and 750%, respectively. The results indicate that UVB-induced increases in apoptosis in the epidermis of wild-type mice are predominantly (but not entirely) by p53- and Bax-dependent pathways and that topical application of caffeine can enhance UVB-induced increases in apoptosis by p53- and Bax-independent pathways.
将雄性或雌性p53(-/-) C57BL/6J小鼠及其野生型同窝小鼠剃毛后，用UVB（60 mJ/cm(2)）照射一次。在暴露于UVB后6 - 10小时，p53(-/-)小鼠中UVB诱导的凋亡性晒伤细胞增加量仅为UVB处理p53(+/+)小鼠后观察到的增加量的10% - 30%。在雌性p53(+/+)或p53(-/-)小鼠中，UVB照射后立即局部应用咖啡因，6小时后分别使UVB诱导的凋亡性晒伤细胞增加量提高了127%和563%。在另一项研究中，将雌性Bax(-/-) C57BL/6J小鼠及其野生型同窝小鼠剃毛后，用UVB（60 mJ/cm(2)）照射一次。在暴露于UVB后6小时，Bax(-/-)小鼠中UVB诱导的凋亡性晒伤细胞增加量仅为UVB处理Bax(+/+)小鼠后观察到的增加量的14%。在Bax(+/+)或Bax(-/-)小鼠用UVB照射后立即局部应用咖啡因，6小时后分别使UVB诱导的凋亡性晒伤细胞增加量提高了214%和467%，并且在Bax(+/+)或Bax(-/-)小鼠用UVB照射后立即局部应用咖啡因，6小时后分别使UVB诱导的caspase 3（活性形式）阳性细胞增加量提高了253%和750%。结果表明，UVB诱导的野生型小鼠表皮细胞凋亡增加主要（但不完全）通过p53和Bax依赖性途径，并且局部应用咖啡因可通过p53和Bax非依赖性途径增强UVB诱导的细胞凋亡增加。
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