Determination of the spectrum of mutations induced by defined-wavelength solar UVB (313-nm) radiation in mammalian cells by use of a shuttle vector.
Mutations induced by UVB (313-nm) radiation, a wavelength in the region of peak effectiveness for sunlight-induced skin cancer in humans, have been analyzed at the sequence level in simian cells by using a plasmid shuttle vector (pZ189). We find that significant differences exist between the types of mutations induced by this solar wavelength and those induced by nonsolar UVC (254-nm) radiation. Compared with 254-nm radiation, 313-nm radiation induces more deletions and insertions in the region sequenced. In addition, although the types of base substitutions induced by the two wavelengths are broadly similar (in both cases, the majority of changes occur at G-C base pairs and the G-C to A-T transition is predominant), an analysis of the distribution of these base changes within the supF gene following irradiation at 313 nm reveals additional hot spots for mutation not seen after irradiation at 254 nm. These hot spots are shown to arise predominantly at sites of mutations involving multiple base changes, a class of mutations which arises more frequently at the longer solar wavelength. Lastly, we observed that most of the sites at which mutational hot spots arise after both UVC and UVB irradiation of the shuttle vector are also sites at which mutations arise spontaneously. Thus, a common mechanism may be involved in determining the site specificity of mutations, in which the DNA structure may be a more important determinant than the positions of DNA photoproducts.
Keyse
S M
SM
Swiss Institute for Experimental Cancer Research, Epalinges.
Amaudruz
F
F
Tyrrell
R M
RM
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000235:genetics; D005822:Genetic Vectors / Q000528:radiation effects*; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D013472:Sunlight; D014162:Transfection / Q000528:radiation effects*; D014466:Ultraviolet Rays