A tobacco-specific N-nitrosamine orcigarette smokecondensate causes neoplastic transformation ofxenotransplanted human bronchial epithelial cells (tobacco smoke/human cells/lung/bronchus/carcinogenesis)

ABSTRACT Usingaxenotransplantation systemin whichimmortalizednontumorigenichumanbronchialepithelial cells(BEAS-2Bcells) aregrownindeepithelialized rattracheasthatare subcutaneously transplanted into athymic nudemice, weexposedBEAS-2Bcells eithertocigarettesmokecondensateorto the tobacco-specific N-nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone. After 6 mothe carcinogen-exposedBEAS-2B cells were neoplastically transformed to invasiveadenocarcinomas. Celllinesobtainedfromxenograftsexposedin vivo to chemicals exhibited several features typical ofma-lignantlungcancercells, suchasincreasedin vivoinvasivenessthat correlated well with enhanced type IV collagenolyticactivity, resistance to serum-induced growth inhibition, andincreased expression oftransforming growthfactor aanditscellular-membranereceptor. Invasiveness,similartothatseenafterexposuretophorbolesters, wasalsodetectedafterin vitroexposure of BEAS-2B cells to cigarette smoke condensate. Collectively, these data indicate that cigarette smokeconden-sate and N-nitrosamine