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Altered p53 Gene Structure and Expression in Human Epithelial Cells after Exposure to Nickel¹

Department of Toxicology, National Institute of Occupational Health, P. O. Box 8149 Dep, 0033 Oslo 1, Norway [L. M., D. R., A. H.], and Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892 [R. A. M., W. P. B., C. C. H.]

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.

¹ This work was supported by the Norwegian Research Council for Science and the Humanities and the Norwegian Cancer Society.

² To whom requests for reprints should be addressed.

Received 9/ 3/91. Accepted 11/ 8/91.

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