Altered p53 gene structure and expression in human epithelial cells after exposure to nickel.
The carcinogenicity of certain nickel compounds is well known. We have previously shown that human kidney epithelial cells were immortalized by treatment with Ni(II) and in cooperation with the v-Ha-ras oncogene transformed the cells to acquire tumorigenicity in athymic nude mice. Immunocytochemistry and sequence analysis of DNA from the nickel-immortalized cells revealed abnormal p53 expression and a T----C transition mutation in codon 238. These data are consistent with the hypothesis that Ni(II)-induced mutation in the p53 gene can be involved in the escape from senescence of kidney epithelial cells.
Maehle
L
L
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Metcalf
R A
RA
Ryberg
D
D
Bennett
W P
WP
Harris
C C
CC
Haugen
A
A
D002461:Cell Line, Transformed; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D004848:Epithelium / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D009154:Mutation / Q000235:genetics*; D009532:Nickel / Q000633:toxicity*
D009532:Nickel