Alterations of protein kinase C, 8-hydroxydeoxyguanosine, and K-ras oncogene in rat lungs exposed to passive smoking

To investigate the effects of exposure to sidestream cigarette smoke (CS) o n the initiation and promotion of lung cancer, two groups of 8 or 10 rats w ere exposed to CS for a 1 h period twice a day for 8, 12, or 20 weeks. The protein kinase C (PKC) activity of the lung exhibited significant changes o f 120, 86 and 81% in the CS groups, compared with the respective control gr oup values in the three exposure periods. The in vitro activation of PKC by the active oxygens was efficiently eliminated by hydroxyl radical scavenge rs, indicating that hydroxyl radicals are responsible for the PKC activatio n. For the alterations in the lung nucleus caused by passive smoking, the 1 2- and 20-week exposure CS groups showed significant increases in the accum ulation of 8-hydroxydeoxyguanosine. One rat with K-ras activation by G:C tr ansversion (GGT-->GCT) at codon 12 was found among 26 rats of the CS groups in the three exposure periods. These results show that active oxygens intr oduced by passive smoking may contribute to K-ras activation as an initiato r of a tumor model, possibly through the oxygen-induced DNA damage, and may also contribute to an initial activation and the subsequent down-regulatio n of PKC as a promoter. (C) 1999 Elsevier Science B.V. All rights reserved.