PDGF AA as mediator in nicotine-dependent carcinogenesis

Effect of nicotine on PDGF AA and PDGF BB interaction with cervicalcancer SiHa cells was tested. [¹²⁵I]PDGF AA was internalizedby cells and accumulated in the cytoplasm and nucleus (chromatin).In the absence of nicotine, maximal accumulation of [¹²⁵I]PDGFAA inside the cells occurred after 1 day of incubation, whichwas followed by a progressive degradation of the growth factorduring the next 2, 3 and 5 days of cell exposure. In the presenceof 0.001 or 0.01% nicotine, accumulation of [¹²⁵I]PDGF AA wasslightly higher than in the absence of nicotine, and maximalaccumulation occurred after 2 days of incubation. In the presenceof 0.1% nicotine, maximal accumulation occurred after 5 daysof incubation and was 20 and 14 times higher in the cytoplasmand chromatin, respectively. Nicotine-postponed degradationand increased nuclear accumulation of PDGF AA resulted in activationof RNA synthesis and cell proliferation. PDGF BB, which wasnot internalized by cells did not respond to nicotine treatment.The proposed mechanism of nicotine-PDGF AA co-carcinogenesismay involve inhibition of growth factor degradation at the lysosomallevel and an increased chromatin accumulation of the non-degradedPDGF.