Cytogenetic and molecular genetic analysis of tumorigenic human bronchial epithelial cells induced by radon alpha particles

To establish a cell culture model for lung carcinogenesis, independentpopulations of the human papillomavirus 18-immortalized human bronchialepithelial cell line BEP2D were treated with high linear energy transferradon-simulated alpha-particles, expanded and xenotransplanted into Nu/Numice. Six independent cell lines were established from tumors thatdeveloped from three separate radiation treatments as follows: treatment(Tx) 1 (30 cGy--two doses), H2BT, Tx 2 (30 cGy-- single dose), R30T1L,R30T2 and R30T3L, Tx 3 (30 cGy--single dose), H1ATN and H1ATBA1.Cytogenetic analysis revealed common changes in all tumor lines: loss ofthe Y chromosome (ch), one of three copies of ch8, one of three copies ofch14, and one of two copies of ch4p16-pter and ch11p15-pter. Analysis ofpolymerase chain reaction-amplified short tandem repeats of informativeloci confirmed the loss of chY in all lines and loss of heterozygosity(LOH) at eight loci spanning the length of ch8 in all lines from Tx's 1 and2. Our data support previous studies indicating the presence of tumorsuppressor genes on ch8. LOH also was confirmed on ch14 at locus D14S306 inall cell lines from Tx 2 and in one of two lines from Tx 3. This region,14q12-q13, may contain changes in one of the five known somatostatinreceptor genes (SSTR1). No LOH was detected at any of the informative locitested for on ch4 or ch11.