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Auto Accidents. Personal Injury. Our Firm. Advice Articles , Personal Injury. Beta-Carotene and Lung Cancer. James Loren November 9, pm. Is there a connection between Beta-Carotene and lung cancer? What is Beta-Carotene?

What is the Relationship between Lung Cancer and Beta-Carotene? What are the Symptoms of Lung Cancer? Persistent cough: A chronic or persistent cough that does not seem to go away is one of the most common.

Pay attention, especially if the cough is accompanied by blood or mucus. Shortness of breath: Lung cancer can cause obstruction or inflammation in the airways, leading to difficulty breathing or shortness of breath.

This symptom may worsen as the cancer progresses. Chest pain: Lung cancer can cause chest pain that may feel sharp or dull. This pain can be constant or intermittent and may worsen with deep breathing, coughing, or laughing.

Fatigue and weakness: Feeling constantly tired and lacking energy can be a sign of lung cancer. This can occur due to the cancer itself or the body's immune response to fighting the disease. Unexplained weight loss: Weight loss without any intentional changes in diet or physical activity can be a red flag for various health conditions, including lung cancer.

Unexplained weight loss is often associated with advanced stages of the disease. Hoarseness or voice changes: If you notice a persistent hoarseness or changes in your voice that last for more than a few weeks, it's important to get it evaluated. Lung cancer can affect the vocal cords and lead to voice changes.

Persistent infections: Frequent respiratory infections, such as bronchitis or pneumonia, can be a sign of an underlying lung condition, including lung cancer. These infections may be difficult to treat and keep reoccurring.

Clubbing of the fingers: Clubbing refers to the abnormal enlargement of the fingertips, often associated with lung cancer. This occurs due to changes in the oxygen levels in the blood. What Does the Research Say About Beta-Carotene and Lung Cancer?

What Should You Do if Taking Beta-Carotene Supplements? Consult with your healthcare provider: Before starting any dietary supplements, including beta-carotene, it's important to consult with your healthcare provider.

They will be able to assess your individual risk factors and determine whether beta-carotene supplements are appropriate for you. Focus on a balanced diet: Instead of relying on supplements, aim to obtain beta-carotene through a varied and balanced diet.

Fruits and vegetables like carrots, sweet potatoes, kale, spinach, and apricots are excellent sources of natural beta-carotene. The confusion regarding carotenoid anticarcinogenic efficacy may be attributed in part to a poor understanding of the interactions between cigarette smoke components, β-carotene and lung epithelial cells.

Cigarette smoke contains high concentrations of two distinctly different populations of free radicals, one in the tar component and the other in gas phase smoke.

The tar component is defined as the material that is trapped by a Cambridge filter that retains Tar consists primarily of an amorphous mixture of polycyclic hydrocarbons, polyphenols and quinones and is strongly reducing in its overall redox character 6 , 7.

Cigarette smoke thus poses a mixed oxidative challenge to the cells. While the strong oxidants in gas phase smoke can rapidly initiate lipid, DNA and protein oxidation, the polyphenol—quinone redox couples in tar can more slowly generate radicals over a sustained period.

These β-carotene peroxyl radicals generated could facilitate β-carotene autoxidation and react with other molecules to produce prooxidant effects. An attractive hypothesis that was put forth to explain the results of the CARET and ATBC trials was that β-carotene may be acting as a prooxidant in the lungs of smokers The basis of this hypothesis was that smoke-borne oxidants, including peroxyl radicals and nitrogen oxides, could initiate β-carotene autoxidation at the relatively high oxygen tension in the lung torr.

This could lead to a secondary oxidation of lung biomolecules by β-carotene and smoke-derived radical intermediates. The resulting prooxidant interaction of β-carotene with smoke could enhance oxidative injury beyond that caused by smoke alone.

A previous study from our laboratory examined the interactions of β-carotene and cigarette smoke in model systems This study identified 4-nitro-β-carotene as a unique product of the reactions between β-carotene and cigarette smoke. It also demonstrated that β-carotene failed to produce a prooxidant interaction with cigarette smoke in liposomal model systems.

The aim of the present study was to extend the findings of the previous research to living cells. Here we have examined the possible prooxidant or antioxidant actions of β-carotene in immortalized human bronchial epithelial cells exposed to cigarette smoke.

Immortalized human bronchial epithelial cells BEAS-2B were obtained from the American Type Culture Collection Rockville, MD. All- trans -β-carotene was obtained from Fluka Chemical Corp.

Ronkonkoma, NY. d -α-Tocopherol was a gift from Henkel Fine Chemicals LaGrange, IL. N , O -bis trimethylsilyl trifluoroacetamide BSTFA and trimethylchlorosilane were from Pierce Rockford, IL. Research grade cigarettes 1R3 were provided by the University of Kentucky Tobacco and Health Research Institute Lexington, KY.

Cambridge filter pads were from Performance Systematics Caledona, MI. All other chemicals were of the highest purity available. Cells were grown on plastic flasks, removed by brief trypsinization, and cells were plated on 25 mm diameter polyester filter supports with a 3 μm pore size Transwell-Clear; Corning Costar, Cambridge, MA , which were inserted into 6-well culture dishes.

Two different methods of β - carotene delivery to BEAS-2B cells were investigated. Cells were exposed to β-carotene solubilized in tetrahydrofuran THF and ethanol. Cells were also exposed to β-carotene incorporated into DPPC liposomes. THF was passed through alumina to remove peroxides prior to use.

The amount of THF or ethanol in the medium never exceeded 0. In the liposome delivery method appropriate volumes of β-carotene stock in hexane and DPPC dissolved in chloroform were evaporated under nitrogen and resuspended in THF and ethanol 0.

Liposomes were produced by injecting the lipid and β-carotene suspension into a flask containing KGM with rapid vortex mixing for final concentrations of μM DPPC and 0. In both modes of delivery 4 ml of β-carotene-supplemented medium was added to the basolateral 2.

The cells were exposed to β-carotene-supplemented culture medium for 24 h prior to cigarette smoke exposure studies. Control cells received equivalent amounts of DPPC liposomes or THF and ethanol without β-carotene.

For smoke exposure experiments cell medium was aspirated from the Transwells and the cells were rinsed with phosphate-buffered saline PBS , pH 7. Two milliliters of PBS was added to the basolateral site of each well. To facilitate interaction of gas phase smoke with BEAS-2B cells no fluid was added to the apical compartments.

The Transwells were placed in glass chambers with separate inlets for compressed air and cigarette smoke. Cells were exposed to ml of gas phase smoke every 10 min using a smoking apparatus consisting of a 60 ml syringe, a three-way stopcock and an inline filter.

Smoke from research grade 1R3 cigarettes was passed through a Cambridge glassfiber filter to remove the tar fraction prior to introduction of smoke into the chamber.

The chamber was purged with fresh compressed air prior to each smoke exposure. These experiments were conducted using an oxygen tension of torr for the cigarette smoke and air mixture to approximate the conditions to which the lung epithelium would be exposed in vivo.

After treatment the cells were rinsed with PBS and subsequently lysed with 10 μmol SDS. Butylated hydroxytoluene BHT, nmol, 22 μg was added to the cell suspension as an antioxidant to prevent adventitious oxidation of β-carotene. The hexane extracts were pooled and evaporated in vacuo. α-Tocopherol propionate was added as an injection standard, the samples were redissolved in mobile phase and analyzed by reverse phase HPLC with diode array detection Hewlett Packard, Palo Alto, CA.

β-Carotene was detected at nm and α-tocopherol propionate at nm. LDH release from the cells was quantified using a LD-L 10 kit Sigma, St Louis, MO. The pooled chloroform fractions were evaporated under nitrogen and redissolved in methanol 1.

Glutathione content of cells was determined using the procedure of Fariss and Reed The procedure involved initial formation of S -carboxymethyl derivatives of free thiols followed by conversion of free amino groups to 2,4-dinitrophenyl derivatives and separation by ion exchange HPLC using γ-glutamyl glutamate as an internal standard.

For α-tocopherol depletion experiments KGM cell medium was supplemented with 1. For α-tocopherol analyses cells were sonicated in a mixture of ethanol 2 ml , α-tocopherol- d 6 internal standard, 10 nmol and SDS 10 μmol.

The samples were extracted with hexane and the hexane extracts were evaporated under N 2. β-Carotene and its smoke oxidation products were analyzed by liquid chromatography—mass spectrometry using an Allsphere ODS-2 5 μm HPLC column 4.

The conditions were maintained until 25 min. MS analyses were performed on a Finnigan TSQ triple quadrupole mass spectrometer using an atmospheric pressure chemical ionization source Finnigan MAT, San Jose, CA.

Mass spectra were obtained in negative ion mode. Results are expressed as means ± SEM. Statistical significance within sets of data was determined by one way analysis of variance ANOVA followed by individual comparisons using Bonferroni's correction for factorial analysis of variance.

Since β-carotene is a highly lipophilic compound poorly taken up by cells in culture, preliminary experiments were conducted to optimize its uptake by BEAS-2B cells.

Despite published reports 17 , 18 , addition of β-carotene in ethanol to culture medium was not found to be a good delivery method due to the limited solubility of β-carotene in ethanol data not shown.

We investigated the uptake of β-carotene by: i exposure of cells to β-carotene solubilized in THF and ethanol; ii exposure of cells to β-carotene incorporated into DPPC liposomes. Addition of β-carotene solubilized in THF and ethanol was consistently found to result in higher uptake by BEAS-2B cells as compared with β-carotene incorporated into liposomes for delivery into the cells Figure 1.

β-Carotene levels in cells decreased over time, suggesting that β-carotene was associated with the cells in a physiologically relevant manner and could participate in the oxidation chemistry of the cells.

Prior to testing our hypothesis that smoke-driven β-carotene autoxidation exerted prooxidant effects it was necessary to establish that gas phase smoke was capable of oxidizing cellular β-carotene. BEAS-2B cells supplemented with an extracellular concentration of 1.

To determine whether smoke-driven autoxidation of β-carotene resulted in prooxidant effects in BEAS-2B cells we investigated the effects of β-carotene on gas phase smoke-induced lipid peroxidation of membrane lipids.

Gas phase smoke exposure significantly enhanced lipid peroxidation in BEAS-2B cells, as assessed by formation of 9'-OH MeLin Figure 4. However, supplementation of the cells with β-carotene did not cause an enhancement of smoke-induced lipid peroxidation.

Overall, β-carotene supplementation led to a slight attenuation of lipid peroxidation levels in BEAS-2B cells at 2. Membrane damage to BEAS-2B cells by exposure to gas phase smoke was assessed by measuring the release of the cytoplasmic enzyme LDH into the medium. Exposure of cells to gas phase smoke resulted in a significant loss of membrane integrity, as indicated by the amount of LDH released by the cells Figure 5.

β-Carotene supplementation did not affect viability of the cells. Moreover, supplementation of cells with β-carotene did not affect the extent of membrane damage caused by gas phase smoke. We then examined the possibility that smoke-driven β-carotene autoxidation was accelerating the rates of depletion of endogenous cellular antioxidants.

Water-soluble glutathione and lipid-soluble α-tocopherol were the representative antioxidants studied. In the case of glutathione gas phase smoke caused rapid depletion of endogenous glutathione levels in BEAS-2B cells Figure 6.

Supplementation of the cells with β-carotene did not enhance this rate of smoke-driven glutathione depletion. Since the cells were grown in serum-free medium, their endogenous levels of α-tocopherol were very low. Hence, we supplemented the cells with 1. In contrast to glutathione, cellular α-tocopherol was much more resistant to gas phase smoke autoxidation Figure 7.

No statistically significant depletion of cellular α-tocopherol levels was observed during the 5 h smoke exposure, even though there was a general trend towards decreased levels.

Although the levels of α-tocopherol appear slightly lower in β-carotene-supplemented cells, the differences were not statistically significant. Position statement - Beta-carotene and cancer risk.

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Beta-carotene β-carotene is a type of carotenoid, an important precursor to vitamin A. Vitamin A is essential for biochemical and physiological processes in the body including vision, reproduction, cellular differentiation and immunity.

β-carotene can be obtained from dark-green leafy vegetables and some not all yellow and orange coloured vegetables and fruits, as well as dietary supplements. There appears to be a marked interaction between β-carotene, smoking and genotype.

Studies have shown there is a convincing association between β-carotene supplements and an increased risk of lung cancer in current smokers.

β-carotene supplements are unlikely to have a substantial effect on the risk of prostate and non-melanoma skin cancers. However, foods containing carotenoids are associated with a probable reduced risk of lung, mouth, pharynx, and larynx cancer.

Dietary β-carotene probably reduces the risk of oesophageal cancer and is unlikely to have a substantial effect on the risk of prostate and non-melanoma skin cancers.

Cancer Council supports the Australian Dietary Guidelines that recommend eating plenty of fruit and vegetables, and the population recommendation of at least two serves of fruit and five serves of vegetables daily. People should eat a wide variety of fruit and vegetables, including a range of different coloured fruit and vegetables, to obtain maximum benefits.

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