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The protective effect of combined an...

Kim, Yuri.

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The protective effect of combined antioxidants (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation against chemical carcinogen (NNK)-induced lung carcinogenesis in smoke-exposed ferrets.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The protective effect of combined antioxidants (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation against chemical carcinogen (NNK)-induced lung carcinogenesis in smoke-exposed ferrets./
Author:	Kim, Yuri.
Description:	226 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-03, Section: B, page: 1405.
Contained By:	Dissertation Abstracts International66-03B.
Subject:	Health Sciences, Nutrition. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3166798
ISBN:	0542024047

The protective effect of combined antioxidants (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation against chemical carcinogen (NNK)-induced lung carcinogenesis in smoke-exposed ferrets.
Kim, Yuri.

The protective effect of combined antioxidants (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation against chemical carcinogen (NNK)-induced lung carcinogenesis in smoke-exposed ferrets. - 226 p.

Source: Dissertation Abstracts International, Volume: 66-03, Section: B, page: 1405.

Thesis (Ph.D.)--Tufts University, 2005.

Research into dietary chemoprevention against lung carcinogenesis has been limited by the lack of appropriate animal models that closely mimic smoking-related human lung cancer. Therefore, many scientists have tried to develop an appropriate model to study lung cancer. The Ferret offers an excellent model for mimicking the condition of the carotenoid intervention studies in smokers, considering the similarities between ferret and human in terms of carotenoid absorption, metabolism, tissue distribution and levels and biological function. The failure of the beta-carotene (BC) intervention trials to show a benefit against lung carcinogenesis and demonstration of a harmful effect of large doses of BC in smokers has shifted interest from the use of single nutrients to nutrient combinations found in food (particularly in fruits and vegetables) for chemoprevention. Possible interaction among BC, alpha-tocopherol (AT), and ascorbic acid (AA) in terms of mutual beneficial protection against oxidative damage raised a hypothesis that using combination of these antioxidants could be more advantageous than using a single antioxidant alone, particularly for smoke related lung cancer.

ISBN: 0542024047Subjects--Topical Terms:

1017801
Health Sciences, Nutrition.

The protective effect of combined antioxidants (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation against chemical carcinogen (NNK)-induced lung carcinogenesis in smoke-exposed ferrets.
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100 1 $a Kim, Yuri. $3 1905081
245 1 4 $a The protective effect of combined antioxidants (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation against chemical carcinogen (NNK)-induced lung carcinogenesis in smoke-exposed ferrets.
300 $a 226 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-03, Section: B, page: 1405.
500 $a Adviser: Xiang-Dong Wang.
502 $a Thesis (Ph.D.)--Tufts University, 2005.
520 $a Research into dietary chemoprevention against lung carcinogenesis has been limited by the lack of appropriate animal models that closely mimic smoking-related human lung cancer. Therefore, many scientists have tried to develop an appropriate model to study lung cancer. The Ferret offers an excellent model for mimicking the condition of the carotenoid intervention studies in smokers, considering the similarities between ferret and human in terms of carotenoid absorption, metabolism, tissue distribution and levels and biological function. The failure of the beta-carotene (BC) intervention trials to show a benefit against lung carcinogenesis and demonstration of a harmful effect of large doses of BC in smokers has shifted interest from the use of single nutrients to nutrient combinations found in food (particularly in fruits and vegetables) for chemoprevention. Possible interaction among BC, alpha-tocopherol (AT), and ascorbic acid (AA) in terms of mutual beneficial protection against oxidative damage raised a hypothesis that using combination of these antioxidants could be more advantageous than using a single antioxidant alone, particularly for smoke related lung cancer.
520 $a In the present study, we have conducted an animal study to investigate whether combined BC (equivalent to 12 mg/day in the human), AT (&sim;100 mg/day), and AA (&sim;210 mg/day) supplementation (AOX) prevents against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis in smoke-exposed (SM) ferrets. Ferrets were treated for six months in the following four groups: (a) Control (n = 9); (b) Control + AOX (n = 9); (c) SM + NNK (n = 12); and (d) SM + NNK + AOX (n = 14).{09}In the present study, we successfully established the ferret as a lung cancer model by using the combination of smoke-exposure with NNK. The histopathological types of tumors including squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma occurring in ferret lungs are very similar to those of humans. In addition, results showed that (1) the AOX supplementation prevented the reduction of lung concentrations of BC and retinoic acid (RA) in the SM + NNK groups of ferrets; (2) AOX supplementation inhibited significantly the SM + NNK induced phosphorylation of Jun N-terminal kinase (JNK), extracellular-signal-regulated protein kinase (ERK); (3) AOX supplementation inhibited significantly the SM + NNK induced upregulation of total p53, phospho p53, Bax, and proliferating cellular nuclear antigen proteins in the lungs of ferrets; and (4) the AOX supplementation decreased both preneoplastic lesion (33%) and tumor formation (36%) in the SM + NNK treated group of ferrets, although these changes were not statistically significant (possibly due to small sample size). These data indicate that the combination of these three antioxidants can protect against lung carcinogenesis by inhibiting the activation of mitogen-activated protein kinase (MAPK) pathways, phosphorylation of p53 and cell proliferation. Furthermore, our data indicate that AT and AA can prevent the smoke-enhanced degradation of BC, thereby facilitating the conversion of BC into RA. Therefore, the results from this thesis research will provide important and useful information for public health concerning protective supplementation of antioxidant vitamins (BC, AT, and AA) against risk of lung cancer, and for understanding the molecular mechanisms of lung carcinogenesis caused by tobacco smoke.
590 $a School code: 0234.
650 4 $a Health Sciences, Nutrition. $3 1017801
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Chemistry, Biochemistry. $3 1017722
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710 2 0 $a Tufts University. $3 1017847
773 0 $t Dissertation Abstracts International $g 66-03B.
790 1 0 $a Wang, Xiang-Dong, $e advisor
790 $a 0234
791 $a Ph.D.
792 $a 2005
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3166798