Study On Initiation Of Human Lung Carcinogenesis

Carcinogenesis is a multistage process composed of initiation, Promotion and progression. Initiation of Carcinogenesis is the irreversible change of cellular DNA induced by carcinogeneic agents that make a cell acquire carcinogeneic potential. The initiation is the key to what is seen in promotion and would play a central role in the long process during carinogenesis , Lung cancer, caused by environmental etiological agents , is a common kind of fatal cancer, primary prevention is not a practicable method in lung cancer control and little knowledge of the molecular events has been accumulated that underlying the pathogenesis of this disease . Exploration of molecular events and molecular biomarkers, that contribute to the initiation of lung cancer and are induced by environmrntal etiological agents , may lay foundation of molecular mechanisms of lung carcinogenesis and early screening of lung cancer . Thus a bright future of restraining the initiation of lung carcinogenesis from progress can be anticipated. Briefly the following results, conclusions and viewpoints are involved in this dissertation. 1, Human fetal lung (HFL) explants, exposed to 100 ug/ ml of Cigarette Smoking Condensate (CSC) and 7 ul/ ml of N -nitrosodiethylamine (DEN) respectively for 24 hours, and continuously cultured 12 days, showed hyperplasia of bronchial epithelium with cellular atypia. DNA from HFL explants exposed to 100 ug/ ml of CSC, 7 ul/ ml of DEN and 100 ug/ ml of N-nitroso-N-methylurea (MNU) respectively for 24 hours, 6 hours and 5 hours, transformed Rat-1 cells and make them form tumors. From these we concluded : i. DEN, CSC and MNU induced irreversible transforming ability of HFL; ii. DEN and CSC made epithelial cells of bronchioles in HFL explants acquire carcinogenic potential. Thus CSC and DEN initiated lung carcinogenesis. The initiation induced by CSC provided direct evidence for lung carcinogenesis caused by cigarette smoking.