This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kramata, P. Articles by Conney, A. H. Search for Related Content PubMed PubMed Citation Articles by Kramata, P. Articles by Conney, A. H.

Patches of Mutant p53-Immunoreactive Epidermal Cells Induced by Chronic UVB Irradiation Harbor the Same p53 Mutations as Squamous Cell Carcinomas in the Skin of Hairless SKH-1 Mice

Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey

Requests for reprints: Pavel Kramata, 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. Phone: 732-445-3400, ext. 238; Fax: 732-445-0687; E-mail: kramata{at}rci.rutgers.edu.

Treatment of SKH-1 hairless mice with UVB (30 mJ/cm²) twice a week for 20 weeks results in the formation of cellular patches, long before the appearance of tumors, that are visualized in epidermal sheets with an antibody (PAb240) recognizing mutated p53 protein. Direct sequencing analysis of the whole coding region of the p53 gene (exons 2-11) detected one or two mutations in 64.4% of 104 analyzed patches and no mutations in nonstained adjacent normal controls. Homozygous mutation was detected in 22.4% of the mutant patches. Except for two nonsense mutations, all others were missense (exons 4-9) and mostly (95.5%) at the DNA-binding domain. Primer extension analysis of cloned PCR fragments found three of four double-mutated patches harboring different mutations in separate alleles. All mutation hotspots reported earlier in UVB-induced mouse squamous cell carcinomas (SCC) at codons 270 (Arg Cys), 149 (Pro Ser), 275 (Pro Leu and Pro Ser), and 176 (His Tyr) with a frequency of 32.1%, 7.1%, 14.7%, and 3.2% were detected in epidermal patches at a frequency 47.7%, 9.1%, 4.5%, and 2.3%, respectively. Mutations at codons 210 and 191 found in patches at respective frequencies of 8.0% and 4.5% were not previously detected in UVB-induced mouse SCC. In summary, (a) the p53 mutation profile of UVB-induced skin patches and SCC was very similar suggesting that patches are precursor lesions for SCC, (b) a small number of patches harbored mutations that were not before observed in SCC from UVB-treated mice, and (c) about 36% of the patches did not harbor a p53 mutation.

This article has been cited by other articles:

				H. Rebel, N. Kram, A. Westerman, S. Banus, H. J. van Kranen, and F. R. de Gruijl Relationship between UV-induced mutant p53 patches and skin tumours, analysed by mutation spectra and by induction kinetics in various DNA-repair-deficient mice Carcinogenesis, December 1, 2005; 26(12): 2123 - 2130. [Abstract] [Full Text] [PDF]

				P. Kramata, Y.-P. Lu, Y.-R. Lou, J. L. Cohen, M. Olcha, S. Liu, and A. H. Conney 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 Carcinogenesis, November 1, 2005; 26(11): 1965 - 1974. [Abstract] [Full Text] [PDF]