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

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) which 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 the remaining patches did not decrease any 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 irradiation with UVB, twice a week for 20 weeks, inhibited UVB-induced formation of mutant p53 positive patches by approximately 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 micromol) 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.

Effect of Caffeine on the ATR/Chk1 Pathway in the Epidermis of UVB-Irradiated Mice

“…In a recent study, we found that topical applications of caffeine to mice with patches of epidermal cells with one or more UVBinduced p53 mutations enhanced the elimination of these patches of p53-mutant cells (33). Interestingly, caffeine administration had selectivity and enhanced the elimination of cells with a p53 mutation on both alleles to a greater extent than cells with a p53 mutation on only one allele (34).…”

Inhibition of carcinogenesis by tea constituents

“…When tea polyphenols are administered orally, their low bioavailability in the skin may limit the inhibitory effect; the contribution of caffeine present in tea to inhibiting carcinogenesis could become more important. Topical application of EGCG and caffeine to the skin was shown to decrease, by a similar extent, the incidence, multiplicity, and size of tumors induced by UVB treatment in SKH-1 mice [38,39].…”

Stochastic fate ofp53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia

“…S3). Following the initial decline, the number and average clone size plateau, indicating that the proportion of mutant cells in the epidermis remains approximately constant (9,10,27). Therefore, we considered whether the stochastic fate of epidermal progenitor cells could account for these observations.…”