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) on the initiation and promotion of lung cancer, two groups of 8 or 10 rats were 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 of 120, 86 and 81% in the CS groups, compared with the respective control group values in the three exposure periods. The in vitro activation of PKC by the active oxygens was efficiently eliminated by hydroxyl radical scavengers, indicating that hydroxyl radicals are responsible for the PKC activation. For the alterations in the lung nucleus caused by passive smoking, the 12- and 20-week exposure CS groups showed significant increases in the accumulation of 8-hydroxydeoxyguanosine. One rat with K-ras activation by G:C transversion (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 introduced by passive smoking may contribute to K-ras activation as an initiator of a tumor model, possibly through the oxygen-induced DNA damage, and may also contribute to an initial activation and the subsequent down-regulation of PKC as a promoter.
Maehira
F
F
Laboratory of Biochemistry, Department of Health Technology, School of Health Sciences, Okinawa, Japan. fmaehira@med.u-ryukyu.ac.jp
Miyagi
I
I
Asato
T
T
Eguchi
Y
Y
Takei
H
H
Nakatsuki
K
K
Fukuoka
M
M
Zaha
F
F
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004789:Enzyme Activation; D011905:Genes, ras / Q000187:drug effects*; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009154:Mutation; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000975:Antioxidants; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D014028:Tobacco Smoke Pollution; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005979:Glutathione Peroxidase; D011493:Protein Kinase C; D003849:Deoxyguanosine; D005978:Glutathione