Relationship of pulmonary tumorigenesis and junctional communication in mouse lungs

OBJECTIVE: To investigate the relationship between the inhibition of the in situ gap junctional intercellular communication (GJIC) and tumorigenesis in the lung and to seek the application of such relationship to lung caner prevention. METHODS: Four-week-old Kunming mice received urethane for lung tumor initiation, and sodium metabisulfite for promotion. Before/after initiation, certain natural/extracted substances possibly capable of promoting GJIC were applied to the parts of the initiated animals for intervention. By microinjecting the fluorescent tracer, GJIC was gauged in lobes of lungs freshley isolated from parts of animals of each group at the age of 8-12 weeks. All the other animals were sacrificed at the age of 22 weeks for lung tumor examination. The inter-group comparisons of incidence data and multiplicity data (fits) were done by Chi-square test and the two side Student's t test. RESULTS: Much earlier before the lung tumor occurrence the incidence of severe inhibition of in situ GJIC in the lungs of the tumor initition + promotion (urethane + sodium metabisulfite) group has risen from 12.5% of the normal group to 87.5% (P=0.005) and the lung tumor incidence later in the former group was 89.5 %, much higher than that of spontaneous lung tumors of the normal group (15.0%, P<0.001). Dietary supplement of green tea and Fructus Jujubae led the incidences of lung GJIC severe inhibition and lung adenomas decrease to 12.5% and 50.0% (P<0.01), respectively, as compared with the control (urethane + sodium metabisulfite) group. Drinking 0.5% taurine solution for 34 days around the initiation decreased the multiplicity of the in situ lung GJIC severe inhibition and lung adenomas of the contorl (urethane only) group from 1.63 ± 1.19 and 1.37±1.26 to 0.38±0.74 (P<0.05) and 0.52±0.81 (P<0.02), respectively. CONCLUSIONS: Inhibition of in situ GJIC in mouse lungs is causally related to tumorigenesis in this tissue. The in situ GJIC assay in fresh lung speciments can be a novel specific technique to screen drugs/ health products for lung cancer prevention.