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, independent populations of the human papillomavirus 18-immortalized human bronchi al epithelial cell line BEP2D mere treated with high linear energy tra nsfer radon-simulated alpha-particles, expanded and xenotransplanted i nto Nu/Nu mice, Six independent cell lines were established from tumor s that developed 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: los s of the Y chromosome (ch), one of three copies of ch8, one of three c opies of ch14, and one of two copies of ch4pl6-pter and ch11p15-pter, Analysis of polymerase chain reaction-amplified short tandem repeats o f informative loci confirmed the loss of chY in all lines and loss of heterozygosity (LOH) at eight loci spanning the length of ch8 in all l ines from Tx's 1 and 2, Our data support previous studies indicating t he presence of tumor suppressor genes on ch8, LOH also was confirmed o n ch14 at locus D14S306 in all 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 somatostatin receptor genes (SSTR1), No LOH was detect ed at any of the informative loci tested for on ch4 or ch11.