title: Absence of the microsatellite mutator phenotype in human bronchial epithelial cells transformed by alpha particles.
abstract: The immortalized human bronchial epithelial cell line, BEP2D, can become malignantly transformed following its irradiation with alpha particles. Exposed cells progress through a latent period of eight to ten weeks prior to exhibiting malignant properties. The molecular basis for this delay is unclear, however it is thought to involve a manifestation of genomic instability brought on by ionizing radiation. In this study we addressed whether the microsatellite mutator phenotype which arises in cells that lack mismatch repair function could have played a role in the radiation-induced transformation of BEP2D cells. Three cell lines, including BEP2D and two transformed clonal derivatives, H2BT2L and R30T1L, were examined for the presence of the microsatellite mutator phenotype using a selectable reporter system developed in our laboratory. This reporter system is based on the ability of stably transduced cells to restore the reading frame of a hygromycin B phosphotransferase transferase gene rendered out of frame by the insertion of a (CA)(13) repeat tract immediately downstream of the ATG start codon. The parental BEP2D cell line had a relatively low hygromycin B resistant colony formation frequency of 2.36 x 10(-4). This value was similar to the frequencies of two malignantly transformed derivatives H2BT2L (0.996 x 10(-4)) and R30T1L (1.87 x 10(-4)). We therefore conclude that the H2BT2L and R30T1L cell lines are not deficient in their hMSH2, hMLH1, hPMS2 or hMSH3 mismatch repair gene functions, and that other factors orchestrated the alpha particle induced malignant transformation of H2BT2L and R30T1L cells.
authors.affiliation: COLUMBIA UNIV,CTR RADIOL RES,NEW YORK,NY 10032. COLUMBIA UNIV,COLUMBIA COMPREHENS CANC CTR,NEW YORK,NY 10032.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: H
authors.initials: H
authors.lastname: Feng
authors.forename: T
authors.initials: T
authors.lastname: Hei
authors.forename: C
authors.initials: C
authors.lastname: Piao
authors.forename: S
authors.initials: S
authors.lastname: Kahn