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Ultraviolet‐B‐light‐induced mutagenesis of C‐H‐ras codons 11 and 12 in human skin fibroblasts
Author(s) -
Amstad Paul A.,
Cerutti Peter A.
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910630124
Subject(s) - pyrimidine dimer , biology , microbiology and biotechnology , ultraviolet light , guanine , mutagenesis , mutation , genetics , dna , gene , chemistry , dna damage , nucleotide , photochemistry
Mutations in the ras oncogene are detected with a high frequency in non‐melanoma skin cancer. Approximately half of the squamous‐cell carcinomas (SCC) and one third of the basal‐cell carcinomas (BCC) carry mutations at the second position of Ha‐ras codon 12 (GGC to GTC), whereas mutations in Ki‐ras codon 12 occur less frequently. Since the mutations in the Ha‐ras and Ki‐ras oncogenes are located opposite potential pyrimidine dimer sites (C‐C), it is likely that the mutations are induced by ultraviolet radiation present in sunlight. We studied the capacity of ultraviolet B (UVB) light to induce base‐pair changes in Ha‐ras codons 11 and 12 in human skin fibroblasts. UVB induced mostly C to T and G to A transitions and C to A and G to T transversions. The base‐pair change with the highest relative abundance was C to T in the middle position of codon 11 followed by (in diminishing relative abundance) C to A in the middle position of codon 11, G to A and G to T in the middle position of codon 12. The C to T and G to A transitions are compatible with pyrimidine photodimers as pre‐mutagenic lesions, whereas the C to A and G to T transversions could be generated due to the formation of 8‐hydroxyguanine, which is the major oxidation product of guanine. The relative abundance of mutations induced by UVB in Ha‐ras codons 11 and 12 does not correlate with mutations observed in the DNA from non‐melanoma skin cancer, where the G to T transversion in the middle position of codon 12 is selected.