Chemoprevention Of Passive Smoking-Induced Lung Tumors Development In Mice With Dietary Supplementation Of Vitamin E

Incidence of cancer, a catastrophic disease for human being, increased year by year in the world, especially for lung cancer, although massive research work has been devoted to tumor therapy. It is generally understood that smoking is the major cause of lung cancer, a kind of tumor with the supreme incidence and mortality in all kinds of malignant tumors, and tobacco prohibition is undoubtedly the most convincing way for lung cancer prevention, but the fact is that tobacco abuse is now popular in most area around the world. Cancer is so complicated and far away from understood, the key is to clarify the exact mechanism of tumor development, so research on fundamental tumor biology should be promoted with special emphasis on oncogenesis. On the other hand, prevention is absolutely more important and urgent than therapy for cancer, enforcement of chemoprevention in public health may be the most economic and effective strategy to counter tumors nowadays.Cigarette smoke extracts (CSE) and mouse embryonic lung cells (MELC) were prepared individually. After the treatment of exposing MELC to CSE or not with or without vitamin E intervention, proliferation viability, DNA damage and apoptosis were measured in MELC to investigate the cell lesion induced by CSE exposure, as well as the protective effects of vitamin E. The mechanism of CSE-induced cell lesion and vitamin E intervention in MELC were further explored. A passive smoking-induced lung tumor model was established in KM mice by the administration of environmental cigarette smoke exposing or not with or without dietary vitamin E supplementation, and lung tumor incidence and multiplicity in KM mice were monitored to assess the cacinogenecity of passive smoking, as well as the chemopreventive efficacy of vitamin E. Redox balance in serum and DNA damage in lung were measured in KM mice to evaluate the oxidation and genotoxicity of passive smoking, as well as the chemoprevention efficacy of vitamin E against them. Apoptosis and the mechanism of regulation underling were also investigated in lung of KM mice, and the role of oxidative stress, DNA damage and apoptosis in the lung tumor development induced by passive smoking was further explored.It was indicated that: (1) CSE induced proliferation viability inhibition, DNA damage, apoptosis and cell cycle redistribution in MELC, which were significantly reversed to normal levels by Vitamin E intervention.(2) Mitochondrial Cyt c release and Caspase-3 activation, as well as the up-regulation of Bax protein and the down-regulation of Bcl-2 protein in MELC were induced by CSE. Vitamin E was found to be an effective inhibitor of the upstated changes induced by CSE.(3) Passive smoking increased the incidence and multiplicity of lung tumors in KM mice from 5.13% and 0.05 in sham control to 53.33% and 0.78 respectively, which were reduced to 17.78% and 0.18 by daily administration of dietary vitamin E supplementation, thus suggesting a definitely chemopreventive efficacy of vitamin E from passive smoking-induce lung tumors in KM mice.(4) The redox balance in the recycling system of KM mice was destroyed by passive smoking. T-AOC level, VE content and GSH-PX activity were decreased while MDA content, ROS activity, iNOS activity and SOD activity were increased in recycling serum of KM mice after cigarette smoke exposing. The damage in the antioxidation system was partly reversed by daily administration of dietary vitamin E supplementation.(5) DNA damage in the lung organ of KM mice was facilitated by passive smoking, and thereafter obviously reversed to normal level by daily administration of dietary vitamin E supplementation.(6) Apoptosis in the adjacent tissues of lung tumor in KM mice was heavily promoted, compared with normal lung tissues and lung tumor tissues.(7) Compared with normal lung tissue of KM mice, the mRNA expression of Bax, Bad, Apaf-1, C-myc and Cyclin D1 were significantly up-regulated, while significantly down-regulated for Bcl-2 and P53 in the adjacent tissues of lung tumor of KM mice; the mRNA expression of Bcl-2, C-myc and Cyclin D1 were significantly up-regulated, while significantly down-regulated for Bax, P53, Bad and Apaf-1 in lung tumor tissues of KM mice.(8) Compared with normal lung tissue of KM mice, the protein expression of Bax was sharply up-regulated, while down-regulated for Bcl-2 in the adjacent tissues of lung tumor of KM mice; the protein expression of Bax was down-regulated with no changes for Bcl-2 in lung tumor tissue of KM mice.In conclusion, a useful experimental animal model was developed to assess the efficacy of chemopreventive agent, vitamin E against lung tumor induction by passive smoking in KM mice. Passive smoking caused oxidation stress and DNA damage in KM mice, which acted as apoptosis signals. Apoptosis was induced in normal lung cells and simultaneously blocked in lung tumor cells, the regulation of both of the two processes were mediated by several molecules of Bcl-2 family in upstream, as a result, lung tumor was promoted and developed. This is possibly one of the mechanisms underling the development of passive smoking-induced lung tumor in KM mice. The chemopreventive effects of vitamin E from passive smoking-induced lung tumor in KM mice was related to it's powerful property of anti-oxidation.