MOLECULAR CYTOGENETIC ALTERATIONS IN THE EARLY-STAGE AT HUMAN BRONCHIAL EPITHELIAL-CELL CARCINOGENESIS

Lung carcinogenesis is a multi-step process involving activation of on cogenes and inactivation of tumor suppress genes. Many molecular and c ytogenetic alterations occur in the early stages of carcinogenesis. We have developed an effective culture system for human bronchial epithe lial cells and lung cancer cells. Four immortalized human bronchial ep ithelial cell lines were established by transfecting the epithelial ce lls with plasmid DNA containing the early region of SV40. Some molecul ar and cytogenetic alterations, such as 3p-, 2q-, 9p-, c-myc transloca tion t(8;14) (q23; q32). were found in one immortalized bronchial epit helial cell line M when approaching malignant transformation. An incre ase in cell proliferation and decrease of apoptosis were noted in the late passages of the immortalized cell line M. Some molecular cytogene tic alterations were also observed in human primary non-small cell lun g cancers. Molecular cytogenetic alterations during the early stage of carcinogenesis of human bronchial epithelial cells may be useful as b iomarkers for both diagnosis and intermediate endpoint of chemoprevent ion of lung cancer. (C) 1998 Wiley-Liss, Inc.