Carotene randomized double-blind placebo controlled. Primary prevention trials in

Carotene data
it is found that the increase in incidence of lung cancer in those men who
intake beta-carotene found to be even more for those who smoked 20 or more
cigarette per day with higher alcohol consumptions. The Alpha-Tocopherol
Beta-Carotene results and other trails results that published in 1996, beta
carotene and retinol efficacy trials was randomized double-blind placebo
controlled. Primary prevention trials in which combined effect of beta-carotene
and retinal can be determined. The active treatment group has higher risk of
lung cancer than the control group. The relative risk of lung cancer in workers
that are exposed to asbestos was 1.40 and the risk for heavy smokers was 1.42.
In this case the relative risk for heavy smokers in not high who had quite
prior to randomization.

Carotenoids,
lung cancer and smoking habits

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There is an
association between smoking, cancer and coronary artery disease that is
accepted worldwide. Over 1 million cancer deaths occur worldwide due to
cigarette smoking annually and 30% of all deaths by cancer in developed
countries. Due to smoking the risk of atherosclerotic diseases is increased by
50% and the risk of coronary heart disease is become double, also cause
endothelial dysfunction, oxidation of LDL cholesterol with high level of
fibrinogen and adhesion molecules, it also increase the aggregation of blood
platelet level, by reduction of HDL cholesterol it increase the preponderance
of vascular spasm.

The principal
cause of lung cancer is a cigarette smoking in association with less healthy
diet that include less intake of vegetables and fruits and also by lowering the
level of pro-vitamin A carotenoids. Residual confronting by smoking is a
workable explanation for the inverse relationship between cancer risk and
carotenoid intake. So, lower beta-carotene level may due to increase metabolic
turnover in result from oxidative stress induced by cigarette smoking.
Furthermore the history of cigarette smoking is not study in detail. Anyway in
high risk populations the development of lung cancer due to beta-carotene is
still unclear. It is reported that beta-carotene or in combination with ?-tocopherol
and beta-carotene enhance the chances of lung cancer after the supplementations
of 18-48 months. This is suggested that beta-carotene in somehow enhanced the
progress of more advance lung cancer and indicates that it is against the
promotional effect of beta-carotene on lung carcinoma in early stages. 

It is proposed
that cigarette smoke components in presence of high oxygen tension cause
oxidation of beta-carotene in the lungs resulting in pro-oxidant effect. So at
higher level of oxygen about 150 mm Hg as in normal air the carotenoids lost
their antioxidant property and express an autocatalytic with pro-oxidant
effect. The pro-oxidant to anti-oxidant behavior of beta-carotene can be
achieved by lowering the oxygen pressure with addition of vitamin C and vitamin
E. carotenoids might behave as an oxygen carrier from peroxyl radicals for
cellular targets, despite a study performed in which bronchial epithelial cells
of humans did not found direct pro-oxidant effect of smoke caused beta-carotene
oxidation products that suggest composite mechanism for enhanced risk of lung
cancer.

Recently two
larger epidemiological prospective studies suggest the intonation effect of
cigarette smoke and intake of dietary beta-carotene on lung cancer and other
cancers caused by smoking. Mannist¨o examined the association between risk of
lung cancer and consumption of specific carotenoids by using data obtained from
cohort studies performed in North America and Europe. During 7 to 16 years of
study among 399,765 participants only 3,155 participants of lung cancer were
diagnosed.  The estimated amount of
consumption of ß-carotene that is finding out by food frequency questionnaires
is between 1.7 to 6.3 mg/day. So consumption of ß-carotene is not linked with
lung cancer risk in past, current or never in smokers as well.

For the
reduction of lung cancer incidence primary method is to stop smoking. Due to
less success in stopping cigarette use increases the interest in the role of
dietary nutrients in the prevention of lung cancer. Carotenoids are the one of
the class of dietary nutrients that attract attention of people as chemo
preventive substance such as beta-carotene because of their anti-oxidant
properties against lung cancer. Carotenoids maintain anti-oxidant functions and
stop the neoplastic transformation induced by carcinogen, stop lipid oxidation
by plasma membrane, and induce unregulated expression of connexin. These
results suggest that carotenoids have chemo preventive properties against
cancer in human beings. Many group and case control study data shown an inverse
relation between intake of fruits and vegetables and risk of lung cancer
incidence, while many recent studies have cast off doubt on these findings.
Many dietary nutrients have been checked on the risk of lung cancer.

Possible
Mechanisms of Carotenoids affects Lung Carcinogenesis

Beta-carotene
is associated with strong singlet oxygen quenching tendency; it is thought that
it is highly related to lipid peroxidation prevention and in cancer cells and
in other cells inactivation of many metabolically generated free radical
species and also low density circulating lipoproteins. But many of its do not
explained by singlet oxygen quenching. Both transfer of electrons physical
effects as well as chemical reactions like consumption of beta-carotene or
oxidation of beta-carotene are called for inactivating peroxy and alkoxy
radical species, and also superoxide anions. Radicals in additions to
carotenoids for lipid peroxyl radicals could be introduced by the effect of
singlet oxygen on lipid membrane, on nitrogen dioxide, or on thiyl radicals.
The tendency of carotenoids differs to react by these pathways many radicals
and in many different in vitro testing systems. For example, with singlet
oxygen beta-carotene forms an draw besides lycopene undergo electron transfer.
For the inhibition of lipid hydro-peroxide making in homogeneous milieu by the
use of methyl-linoleate and azo compounds the xanthophylls astaxanthin and
canthaxanthine are much better than that of beta-carotene. These
methyl-linoleate and azo compounds have keto group consisting of xanthophylls
that are behave in bilayer membrane as molecular rivets. The chemistry of
carotenoids molecules actions are still under investigations.

The
carotenoids including beta-carotene that are precursors of vitamin A exert
their effect by cleavage to retinol molecule, that stop cell proliferation and
induced differentiation of the epithelial cells by directly bind to nuclear
receptors such as RAR and RXR and also later modifications in gene activity. In
addition to this, carotenoids reported as to modulate cytochrome P450
metabolically that stop arachidonic acid metabolism in which beta-carotene
acted as antioxidant with free radical or as reactive species scavengers;
crocetin, lutein, cryptoxanthin, astaxanthin, canthaxanthine, lycopene,
zeaxanthin alpha-carotene, and beta-carotene; modulators of the immune systems
are beta-carotene, canthaxanthine and astaxanthin; that induced
differentiations of the gap junctions for intercellular communications like
lycopene, astaxanthin, lutein, beta–carotene, canthaxanthine and
alpha-carotene; stop the chromosome damaging and also chromosome instability by
canthaxanthine, beta-carotene; and stop the biochemical changes in association
with cell proliferation that include N-myc expression with beta and
alpha-carotene, guanylate as well as adenylate cyclase activity by
beta-carotene, and ornithine decarboxylase activities by beta-carotene. Cell
apoptosis can be influend by beta-carotene, by which cell death has been done
instead of the cell proliferation. The gene bcl-2 has anti apoptotic effect and
it is also decrease the activity of reactive oxygen species as well as enhances
cell proliferation. These mechanisms can be mediated by alternations in oxidant
or antioxidant balance.

Recommendation for
carotenoids intake and lung diseases

Daily total intake of nutrient
supplementation is given in the table. Out of 18 lavages samples 12 contain
enough number of cells for HPLC analysis. In Table serum, BAL and lung nutrient
level are summarized. The level of carotenoid like a-carotene, f3-carotene,
lycopene, zeaxanthin, and f3-cryptoxanthin, retinol as well as a-tocopherol
level was obtained in all serum and in lung tissue samples. Due to low level of
individual carotenoid in BAL samples the individual carotenoid level is not
determined but total carotenoid level can be obtained. By the use of dietary
questionnaire daily dietary consumption of f3-carotene, retinol, and
a-tocopherol but not of all carotenoids were obtained