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 hotspots, 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.

The derivations of human exposure limits for laser radiation rely heavily upon experimental ocular injury studies. The limits are derived by committees of ophthalmic experts through a review of all available threshold data and an understanding of mechanisms of laser/tissue interaction. A major point of discussion in this derivation process relates to the level of uncertainty of the threshold of injury. An indication of the level of uncertainty relates to the slope of the transformed dose-response curve, or the "probit plot" of the data. The most cited point on the probit plot is the exposure that represents a 50% probability of injury: the ED-50. This value is frequently referred to as the "threshold," even though some experimental damage points exist below this "threshold." An analysis of any number of example data sets reveals that the slope in most experiments cannot be explained by biological variation alone. The optical, thermophysical, and biological factors influencing the probit plot are critically analyzed to provide guidance for deriving exposure limits. By theoretically modeling an experiment, small errors in focus are shown to produce a substantial change in the ED-50 and the slope of the probit plot.