Frequency of ultraviolet radiation-induced mutation at the hprt locus in repair-proficient murine fibroblasts transfected with the denV gene of bacteriophage T4.
The frequency of spontaneous and ultraviolet radiation (UVR)-induced mutation at the hprt locus was determined in control and denV-transfected, repair-proficient murine fibroblasts. Control cells removed an average of 25% of pyrimidine dimers induced by exposure to 150 J/m2 UVR from an FS40 sunlamp within 24 h; under the same conditions of induction and repair, denV-transfected cells removed an average of 71% of pyrimidine dimers. Control cells were somewhat more resistant than denV-transfected cells to killing by UVR. The average frequency of spontaneous mutation at the hprt locus for control and denV-transfected cells was 3 and 15 6-thioguanine (6-TG)-resistant colonies per 10(6) surviving cells, respectively; there was no statistically significant difference between control and denV-transfected cells. However, after exposure to 75 or 150 J/m2 UVR, denV-transfected cells had a significantly lower frequency of mutation to 6-TG resistance. After exposure to a fluence of 75 J/m2, the average frequency of UVR-induced mutation at the hprt locus was 166 mutant colonies per 10(6) surviving cells for control cells and 92 mutant colonies for denV-transfected cells; after 150 J/m2, control cells had 205 6-TG-resistant colonies per 10(6) cells, while denV-transfected cells had 61 mutant colonies. These results demonstrate that UVR-induced pyrimidine dimers are mutagenic photoproducts in mammalian cells.
Kusewitt
D F
DF
Center for Photomedicine, Lovelace Medical Foundation, Albuquerque, NM 87108.
Budge
C L
CL
Anderson
M M
MM
Ryan
S L
SL
Ley
R D
RD
D000818:Animals; D017122:Bacteriophage T4 / Q000201:enzymology / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D051379:Mice; D009154:Mutation; D011740:Pyrimidine Dimers; D014162:Transfection; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers; D007041:Hypoxanthine Phosphoribosyltransferase; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer)