Correlation of UVC and UVB cytotoxicity with the induction of specific photoproducts in T-lymphocytes and fibroblasts from normal human donors.
By using specific monoclonal antibodies in situ and a computer-assisted image analysis system we have determined the relative induction of cyclobutane dimers, (6-4) photoproducts and Dewar isomers in human mononuclear cells and fibroblasts following irradiation with UVC, broad-spectrum UVB and narrow-spectrum UVB. The lamps produced these lesions in different proportions, with broad-spectrum UVB inducing a greater combined yield of (6-4) photoproducts and Dewar isomers per cyclobutane dimer than UVC or narrow-spectrum UVB. The relative induction ratios of (6-4) photoproducts compared to cyclobutane dimers were 0.15, 0.21 and 0.10 following irradiation with UVC, broad- or narrow-spectrum UVB, respectively. Although Dewar isomers were induced by UVC, their relative rate of formation compared to cyclobutane dimers was significantly greater after irradiation with either broad-spectrum or narrow-spectrum UVB. These values were 0.001, 0.07 and 0.07, respectively. With each lamp source, we have determined the survival of normal human T-lymphocytes and fibroblasts at fluences, which induce equivalent yields of cyclobutane dimers, (6-4) photoproducts or (6-4) photoproducts plus Dewar isomers. Killing of fibroblasts appears to be associated with (6-4) photoproduct formation, whereas killing of T-lymphocytes seems to be mediated by combined (6-4) plus Dewar yields. These results emphasize the need to study the biological effects of UVB because cellular responses may be different from those following UVC irradiation.
Clingen
P H
PH
MRC Cell Mutation Unit, Sussex University, Falmer, Brighton, United Kingdom.
Arlett
C F
CF
Cole
J
J
Waugh
A P
AP
Lowe
J E
JE
Harcourt
S A
SA
Hermanova
N
N
Roza
L
L
Mori
T
T
Nikaido
O
O
D000911:Antibodies, Monoclonal; D001666:Binding Sites, Antibody; D002470:Cell Survival / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D011740:Pyrimidine Dimers / Q000096:biosynthesis; D012016:Reference Values; D013601:T-Lymphocytes / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D011740:Pyrimidine Dimers; D004247:DNA