Localization of tumor suppressor gene candidates by cytogenetic and short tandem repeat analyses in tumorigenic human bronchial epithelial cells.

Publisher: Irl Press At Oxford University Press Country of Publication: England NLM ID: 8008055 Publication Model: Print Cited Medium: Print ISSN: 0143-3334 (Print) Linking ISSN: 01433334 NLM ISO Abbreviation: Carcinogenesis Subsets: MEDLINE

Publication: Oxford : Irl Press At Oxford University Press
Original Publication: [New York, IRL Press]

Cocarcinogenesis* ; Genes, Tumor Suppressor* ; Repetitive Sequences, Nucleic Acid*; Bronchi/*chemistry ; Chromosomes, Human, Pair 14/*genetics ; Chromosomes, Human, Pair 8/*genetics ; Lung Neoplasms/*genetics ; Neoplasms, Radiation-Induced/*genetics; Alpha Particles ; Aneuploidy ; Animals ; Bronchi/pathology ; Bronchi/radiation effects ; Bronchi/virology ; Cell Line, Transformed/transplantation ; Cell Transformation, Viral/radiation effects ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human/radiation effects ; Chromosomes, Human, Pair 14/radiation effects ; Chromosomes, Human, Pair 8/radiation effects ; Epithelial Cells/chemistry ; Epithelial Cells/pathology ; Epithelial Cells/radiation effects ; Epithelial Cells/transplantation ; Epithelial Cells/virology ; Genetic Predisposition to Disease ; Humans ; Loss of Heterozygosity ; Lung Neoplasms/etiology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Papillomaviridae/physiology ; Polymerase Chain Reaction ; Radon ; Y Chromosome/radiation effects

Radon exposure is associated with increased risk for bronchogenic carcinoma. Mutagenesis analyses have revealed that radon induces mostly multi-locus chromosome deletions. Based on these findings, it was hypothesized that deletion analysis of multiple radon-induced malignant transformants would reveal common mutations in chromosomal regions containing tumor suppressor genes responsible for malignant transformation. This hypothesis was supported by a previous study in which tumorigenic derivatives of the human papillomavirus 18-immortalized human bronchial epithelial cell line BEP2D were established following irradiation with 30 cGy of high linear energy transfer radon-simulated alpha-particles. Herein, we describe the analyses of 10 additional tumorigenic derivative cell lines resulting from the irradiation of five additional independent BEP2D populations. The new transformants have common cytogenetic changes, including the loss of chromosome (ch)Y, one of three copies of ch8, one of two copies of ch11p15-pter and one of three copies of ch14. These changes are the same as those reported previously. Analysis of PCR-amplified short tandem repeats of informative loci confirmed the loss of heterozygosity (LOH) at 12 loci spanning the length of ch8 in cell lines from four of the total of eight irradiation treatments to date and the loss of chY in all cell lines (8 of 8). LOH analysis with a total of 17 informative loci confirmed loss on ch14 in transformants from seven of eight irradiation treatments and indicated a 0.5-1.7 cM region of common involvement centered around locus D14S306. No LOH was detected at any of the informative loci on ch11. The overall results support our stated hypothesis. Further studies are currently in progress to determine whether the ch8 and ch14 regions contain genes with tumor suppressor function in bronchial epithelial cells.

CA49062 United States CA NCI NIH HHS; ES-05719 United States ES NIEHS NIH HHS; N0I-CB-33063 United States CB NCI NIH HHS

Q74S4N8N1G (Radon)

Date Created: 20000205 Date Completed: 20000403 Latest Revision: 20190513

20231215

10.1093/carcin/21.2.205

10657959