PDGF AA AS MEDIATOR IN NICOTINE-DEPENDENT CARCINOGENESIS

Effect of nicotine on PDGF AA and PDGF BB interaction with cervical ca ncer SiHa cells was tested, [I-125]PDGF AA was internalized by cells a nd accumulated in the cytoplasm and nucleus (chromatin), In the absenc e of nicotine, maximal accumulation of [I-125]PDGF AA inside the cells occurred after 1 day of incubation, which was followed by a progressi ve degradation of the growth factor during the next 2, 3 and 5 days of cell exposure, In the presence of 0.001 or 0.01% nicotine, accumulati on of [I-125]PDGF AA was slightly higher than in the absence of nicoti ne, and maximal accumulation occurred after 2 days of incubation. In t he presence of 0.1% nicotine, maximal accumulation occurred after 5 da ys of incubation and was 20 and 14 times higher in the cytoplasm and c hromatin, respectively, Nicotine-postponed degradation and increased n uclear accumulation of PDGF AA resulted in activation of RNA synthesis and cell proliferation. PDGF BB, which was not internalized by cells did not respond to nicotine treatment. The proposed mechanism of nicot ine-PDGF AA co-carcinogenesis may involve inhibition of growth factor degradation at the lysosomal level and an increased chromatin accumula tion of the non-degraded PDGF.