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Carcinogenesis Advance Access published online on April 7, 2005

Carcinogenesis, doi:10.1093/carcin/bgi086
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Published by Oxford University Press 2005
Received December 22, 2004
Revised March 23, 2005
Accepted March 25, 2005

CARCINOGENESIS

Administration of green tea or caffeine enhances the disappearance of UVB-induced patches of mutant p53 positive epidermal cells in SKH-1 mice

Yao-Ping Lu 1, You-Rong Lou 1, Jie Liao 1, Jian-Guo Xie 1, Qing-Yun Peng 1, Chung S. Yang 1, and Allan H. Conney 1*

1 Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA

* To whom correspondence should be addressed.
Allan H. Conney, E-mail: aconney{at}rci.rutgers.edu


   Abstract

Irradiation of female SKH-1 hairless mice with UVB (30 mJ/cm2) twice a week for 10-20 weeks resulted in the formation of a large number of cellular patches (>8 adjacent cells/patch) that are recognized with an antibody (Pab240) that recognizes mutated but not wild-type p53 protein. These patches are not recognized by an antibody (Pab1620) to wild type p53 protein. The patches, which are considered putative early cellular markers of the beginning of tumor formation, started appearing after 4-6 weeks of UVB treatment, and multiple patches were observed after treatment for 10 weeks. The number and size of the patches increased progressively with continued UVB treatment. Discontinuation of UVB for 4 weeks resulted in an 80-90% decrease in the number of these patches. The number of remaining patches did not decrease further but remained relatively constant for at least 4-9 weeks. Oral administration of green tea (6 mg tea solids/ml) or caffeine (0.4 mg/ml) as the sole source of drinking fluid during twice a week irradiation with UVB for 20 weeks inhibited UVB-induced formation of mutant p53 positive patches by about 40%. Oral administration of green tea (6 mg tea solids/ml) as the sole source of drinking fluid or topical applications of caffeine (6.2 µmoles) once a day 5 days a week starting immediately after discontinuation of UVB treatment enhanced the rate and extent of disappearance of the mutant p53-positive patches.

Topical applications of caffeine to the dorsal skin of mice pretreated with UVB for 20 weeks resulted in enhanced apoptosis selectively in focal basal cell hyperplastic areas of the epidermis (putative precancerous lesions), but not in areas of the epidermis that only had diffuse hyperplasia. Our studies indicate that the chemopreventive effect of caffeine or green tea may occur by a proapoptotic effect preferentially in early precancerous lesions.

Keywords: UVB-induced skin cancer; patches of mutated p53 cells; cancer chemoprevention by tea and caffeine.
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