Cell survival and shuttle vector mutagenesis induced by ultraviolet A and ultraviolet B radiation in a human cell line.
Although it is known that sunlight is carcinogenic,few molecular data are available concerning the mutagenic effects of ultraviolet (UV) B (290-320 nm) and UVA (320-400 nm) radiation in human cells. To analyze the biologic effects of UVA and UVB, we irradiated the 293 human cell line, derived from adenovirus-transformed human embryonic kidney cells, in which we had stably introduced a shuttle vector harboring the lacZ' bacterial gene as the mutagenesis target. Identical cell survival occurred after UVA doses 700-fold higher than UVB. This comparable to the UVA/UVB ratio that reaches the basal cell layer of the skin after sunlight exposure with UVB sunscreen. The frequency of UVA- and UVB- induced mutations increased with the UV dose as cell survival decreased. At cell survival levels greater than 10%, UVA and UVB induced similar frequencies of mutations in the episomal lacZ gene, whereas for cell survival lower than 10%, UVA induced twice as many mutations as UVB. Sequence analysis of 81 independent lacZ mutants (36 UVA- and 45 UVB-induced) revealed specific characteristics for some UV-induced-mutations, particularly for UVB. Mutations at A/T base pairs were induced more frequently by UVA than by UVB. The UVA-induced mutation spectrum that we have observed in human cells may help help to elucidate the mechanism of skin carcinogenesis.
Robert
C
C
Laboratory of Molecular Genetics, Institut de Recherches sur le Cancer, Villejuif, France.
Muel
B
B
Benoit
A
A
Dubertret
L
L
Sarasin
A
A
Stary
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007763:Lac Operon / Q000528:radiation effects*; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D017354:Point Mutation; D013472:Sunlight / Q000009:adverse effects; D014466:Ultraviolet Rays / Q000009:adverse effects*