Spontaneous p53mutation in murine mesothelial cells:increased sensitivity to dna damage induced by asbestos and ionizing radiation

Autor: Cistulli, Cheryl A., Sorger, Thomas, Marsella, Jean M., Vaslet, Charles A., Kane, Agnes B.
Zdroj: Toxicology and Applied Pharmacology; November 1996, Vol. 141 Issue: 1 p264-271, 8p
Abstrakt: The p53gene regulates the GI cell cycle checkpoint in response to DNA damage. A primary murine mesothelial cell line (D9) spontaneously acquired a point mutation at codon 135 in exon 5 of the p53gene, resulting in substitution of alanine for proline; early passage D9 cells expressed wild-type p53. The growth rate of late passage D9 cells that acquired the p53mutation was increased compared to that of early passage cells; however, this mutation was not sufficient to confer tumorigenicity to this cell line. Mammalian cells that express wild-type p53show a transient arrest in G1 after exposure to ionizing radiation. Early passage D9 cells showed a GI arrest following ionizing radiation, while late passage D9 cells arrested in G2 or mitosis. The clastogenic effects of ionizing radiation can be demonstrated by the cytokinesis-arrested micronucleus assay. Following treatment with cytochalasin B to arrest cytokinesis, ionizing radiation induced micronuclei in 50% of late passage D9 cells compared to 15% of early passage cells. After exposure to 15 μg/cm2of crocidolite asbestos fibers, 18% of late passage cells had micronuclei compared to 4% of early passage cells. It is hypothesized that loss of the G1 cell cycle checkpoint contributes to genetic instability in murine mesothelial cells.
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