[ Citation in PubMed ] [ Related Articles ]

Susceptibility of p53 -deficient Mice to Induction of Mesothelioma by Crocidolite Asbestos Fibers

Jean M. Marsella, Brenda L. Liu, Charles A. Vaslet, and Agnes B. Kane

Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, Rhode Island

Abstract
Exposure of mesothelial cells to asbestos fibers in vitro has been shown to induce DNA damage mediated by oxidants. An early cellular response to DNA damage is increased expression of the p53 protein. This protein induces transcription of genes that activate cell cycle checkpoints or induce apoptosis. A murine mesothelial cell line that spontaneously acquired a point mutation in the p53 gene shows increased sensitivity to DNA damage induced by crocidolite asbestos fibers. It is hypothesized that p53 -deficient mice will show increased sensitivity to the genotoxic effects of asbestos and accelerated development of malignant mesotheliomas. -- Environ Health Perspect 105(Suppl 5):1069-1072 (1997)

Key words : p53 tumor suppressor gene, asbestos, mesothelioma

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 27 March 1997; accepted 27 May 1997.
This research was supported by grants R01 ES05712 and R01 ES03721 from the National Institute of Environmental Health Sciences.
Address correspondence to Dr. A.B. Kane, Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, RI 02912. Telephone: (401) 863-1110. Fax: (401) 863-9008. E-mail: agnes_kane@brown.edu
Abbreviations used: TdT, terminal deoxynucleotide transferase; UICC, Union Internationale Contre le Cancer.

[ Table of Contents ] [ Full Article ] [ Citation in PubMed ] [ Related Articles ]

Last Update: October 27, 1997