Journal Article

Effect of administration of caffeine or green tea on the mutation profile in the <i>p53</i> gene in early mutant p53-positive patches of epidermal cells induced by chronic UVB-irradiation of hairless SKH-1 mice

Pavel Kramata, Yao-Ping Lu, You-Rong Lou, Julie L. Cohen, Meir Olcha, Sandy Liu and Allan H. Conney

in Carcinogenesis

Volume 26, issue 11, pages 1965-1974
Published in print November 2005 | ISSN: 0143-3334
Published online June 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi162
Effect of administration of caffeine or green tea on the mutation profile in the p53 gene in early mutant p53-positive patches of epidermal cells induced by chronic UVB-irradiation of hairless SKH-1 mice

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Irradiation of SKH-1 mice with UVB light for 20 weeks resulted in a large number of patches of epidermal cells, which was visualized with an antibody that recognizes mutated p53 protein. Oral treatment of mice with caffeine (0.4 mg/ml) or green tea (6 mg tea solids/ml) as the drinking fluid during UVB irradiation decreased the number of patches by ∼40%. Sequencing analysis of the p53 gene (exons 3 to 9) detected 88, 82 or 39 point mutations in 67, 70 or 29 patches from water, caffeine or tea treated mice, respectively. A major hotspot at codon 270 (Arg→Cys) accounted for 47.7% (water), 70.7% (caffeine) or 46.2% (tea) of all mutations. Patches from caffeine treated mice had fewer types of mutations than patches from mice treated with water or tea. Administration of caffeine or tea during 20 weeks of UVB irradiation eliminated mutations at codons 149 (Pro→Ser) and 210 (Arg→Cys) but increased the frequency of mutations at codon 238 (Ser→Phe). Topical applications of caffeine (1.2 mg in 100 μl acetone) once a day, five times a week for 6 weeks after stopping UVB decreased the number of patches by 63% when compared with mice treated with acetone. DNA sequencing analysis detected 63 and 68 mutations in 48 and 57 patches from acetone or caffeine treated mice, respectively. Although no differences in the frequency, position or types of mutations were observed, the caffeine group harbored less homozygous mutations (12.3% of the total) than the acetone group (31.3% of the total, P = 0.029). In summary, oral treatment of mice with caffeine or green tea during chronic UVB irradiation changed the mutation profile of the p53 gene in early mutant p53 positive epidermal patches, and topical applications of caffeine after discontinuation of chronic UVB irradiation specifically eliminated patches harboring homozygous p53 mutations.

Keywords: CPD, cis–syn cyclobutane pyrimidine dimers; NER, nucleotide excision repair; SCC, squamous cell carcinomas; TLS, translesion replication synthesis.

Journal Article.  7012 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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