Analysis of mutation spectra in UVB-exposed mouse skin epidermis and dermis: frequent occurrence of C-->T transition at methylated CpG-associated dipyrimidine sites.

摘要: We recently reported the kinetics of mutation induction by UVB in skin epidermis and dermis transgenic Muta™ mice [Ikehata Ono, Mutat Res 508:41–47, 2002]. In present study we determined complete DNA sequence lacZ transgene 208 mutants isolated from UVB-irradiated control mice. The resulting patterns for were similar, although two CCTT tandem substitutions, one signature mutations UV insult, detected only among UVB-induced epidermal mutants. spectra both dominated CT transitions (83% 62%); however, irradiated occurred almost exclusively dipyrimidine sites, while those preferred CpG sites. Thus, spectrum tissues was different background UV-specific, confirming utility system studies vivo. An analysis bases adjacent to mutated cytosines revealed that sites 5′-TC-3′ > 5′-CC-3′ 5′-CT-3′. Among mice, recovered frequently at associated with CpG. showed heavily methylated dermis. methylation could contribute recurrent or hotspot mammalian genome. Environ. Mol. Mutagen. 41:280–292, 2003. © 2003 Wiley-Liss, Inc.