While the mutagenic and carcinogenic properties of longwave UV light (UVA) are well established, mechanisms of UVA mutagenesis remain a matter of debate. To elucidate the mechanisms of mutation formation with UVA in human skin, we determined the spectra of UVA-and UVB-induced mutations in primary human fibroblasts. As with UVB, we found the majority of mutations to be C-to-T transitions also with UVA. For both UVA and UVB, these transitions were found within runs of pyrimidines, at identical

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... spots, and with the same predilection for the nontranscribed strand. They also included CC-to-TT tandem mutations. Therefore, these mutations point to a major role of pyrimidine dimers not only in UVB but also in UVA mutagenesis. While some differences were noted, the similarity between the spectra of UVA-and UVB-induced mutations further supports similar mechanisms of mutation formation. A non-dimer type of DNA damage does not appear to play a major role in either UVA or UVB mutagenesis. Therefore, the previously reported increasing mutagenicity per dimer with increasing wavelengths cannot be due to non-dimer DNA damage. Differences in the cellular response to UVA and UVB, such as the less prominent activation of p53 by UVA, might determine a different mutagenic outcome of UVA-and UVB-induced dimers.