Induction of pulmonary neoplasia in the smoke-exposed ferret by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): A model for human lung cancer

Kim, Yuri; Liu, Xiaolong S.; Li, Chun; Smith, Donald E.; Russell, Robert M.; Wang, Xiang Dong

doi:10.1016/j.canlet.2005.03.052

Cited by 28 publications

(32 citation statements)

References 26 publications

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“…This result is consistent with previous studies showing reduced IGFBP-3 expression in lung samples in 57% of lung cancer patients, 53 and an association of reduced IGFBP-3 with the development of both preneoplastic lesions (squamous metaplasia, squamous dysplasia and atypical adenomatous hyperplasia) and neoplastic lesions (squamous carcinoma and adenocarcinoma) in the lungs of ferrets. 7,29 In the present study, neither the plasma IGF-1 concentration nor lung IGF-1 mRNA expression were changed by smoke exposure and NNK treatment (Table III), which confirms previous reports showing a lack of association between circulating IGF-1 and lung cancer in humans 55 or in ferrets. 22 However, plasma concentrations of IGFBP-3 and liver mRNA expression of IGFBP-3 were higher in the ferrets after 6 months of SM1NNK treatment, when compared with those of the control group.…”

Section: Discussionsupporting

confidence: 80%

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The effects of combined antioxidant (β‐carotene, α‐tocopherol and ascorbic acid) supplementation on antioxidant capacity, DNA single‐strand breaks and levels of insulin‐like growth factor‐1/IGF‐binding protein 3 in the ferret model of lung cancer

Kim

Lian

Yeum

et al. 2007

Intl Journal of Cancer

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Insulin‐like growth factor 1 (IGF‐1) and its major binding protein, IGF binding protein 3 (IGFBP‐3) are implicated in lung cancer and other malignancies. We have previously shown that the combination of three major antioxidants [β‐carotene (BC), α‐tocopherol (AT) and ascorbic acid (AA)] can prevent lung carcinogenesis in a 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK)‐treated and smoke‐exposed (SM) ferret model, which is highly analogous to humans. The present study is aimed at determining the effect of the combination of BC, AT and AA on antioxidant capacity, lymphocyte DNA damage, plasma IGF‐1 and IGFBP‐3 concentrations, as well as on IGF‐1/IGFBP‐3 mRNA expression in the tissues (lung and liver) of the ferrets. Ferrets were treated with or without combined antioxidant (BC, AT and AA) supplementation (AOX) for 6 months in the following 4 groups: (i) control; (ii) SM+NNK; (iii) AOX; and (iv) SM+NNK+AOX. Combined AOX supplementation significantly attenuated SM+NNK induced lymphocyte DNA damage in the ferret, while increasing resistance to oxidative damage when challenged with H2O2 in vitro. Ferrets treated with SM+NNK had significantly lower IGFBP‐3 mRNA expression in lungs, whereas there was significantly higher IGFBP‐3 mRNA expression in the liver, as well as higher circulating IGFBP‐3 concentrations. Combined AOX supplementation did not affect the plasma or tissue (lung and liver) ratio of IGF‐1/IGFBP‐3. Combined antioxidant supplementation provides protection against smoke‐induced oxidative DNA damage, but does not affect the IGF‐1/IGFBP‐3 system. Differential expression of IGFBP‐3 in different tissues indicates that caution should be taken when using plasma IGFBP‐3 as a biomarker of tissue status. © 2007 Wiley‐Liss, Inc.

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Section: Discussionsupporting

confidence: 80%

“…7,22,28,29 However, the effects of antioxidants on plasma antioxidant capacity and smoke-induced DNA damage have not been studied in the ferret model.…”

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confidence: 99%

The effects of combined antioxidant (β‐carotene, α‐tocopherol and ascorbic acid) supplementation on antioxidant capacity, DNA single‐strand breaks and levels of insulin‐like growth factor‐1/IGF‐binding protein 3 in the ferret model of lung cancer

Kim

Lian

Yeum

et al. 2007

Intl Journal of Cancer

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“…In ferrets, a combination of monthly injection of 50 mg/kg NNK administered for four consecutive months and daily exposure to cigarette smoke for 6 months resulted in the development of grossly identifiable neoplastic lesions in the lung in 50% of the tested ferrets, with histopathological types of squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma similar to those in humans, while no ferrets in the control group developed any lesions during this time [23]. Aizawa et al [24] also used this scheme in male ferrets (3-5-month old) without smoke exposure.…”

Section: Introductionmentioning

confidence: 99%

Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms

Ge¹,

Xu²,

Chen³

2015

ABBS

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Tobacco usage is a major risk factor in the development, progression, and outcomes for lung cancer. Of the carcinogens associated with lung cancer, tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is among the most potent ones. The oncogenic mechanisms of NNK are not entirely understood, hindering the development of effective strategies for preventing and treating smoking-associated lung cancers. Here, we introduce the NNK-induced lung cancer animal models in different species and its potential mechanisms. Finally, we summarize several chemopreventive agents developed from these animal models.

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“…Although there is convincing evidence that carcinogens contained within cigarette smoke induce lung tumorigenesis (2)(3)(4)(5), additional mechanisms may contribute to the increased cancer risk in smokers.…”

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confidence: 99%

Cigarette Smoke Impairs NK Cell-Dependent Tumor Immune Surveillance

Лу¹,

Zavitz²,

Chen³

et al. 2007

The Journal of Immunology

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In this study, we investigated the impact of cigarette smoke on tumor immune surveillance and its consequences to lung tumor burden in a murine lung metastasis model. Cigarette smoke exposure significantly increased the numbers of lung metastases following B16-MO5 melanoma challenge. This effect was reversible; we observed significantly fewer tumor nodules following smoking cessation. Using RAG2−/− and RAG2−/−γc−/− mice, we provide strong evidence that increased tumor incidence was NK cell dependent. Furthermore, we show that cigarette smoke suppressed NK activation and attenuated NK CTL activity, without apparent effect on activating or inhibitory receptor expression. Finally, activation of NK cells through bone marrow-derived dendritic cells conferred protection against lung metastases in smoke-exposed mice; however, protection was not as efficacious as in sham-exposed mice. To our knowledge, this is the first experimental evidence showing that cigarette smoke impairs NK cell-dependent tumor immune surveillance and that altered immunity is associated with increased tumor burden. Our findings suggest that altered innate immunity may contribute to the increased risk of cancer in smokers.

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Induction of pulmonary neoplasia in the smoke-exposed ferret by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): A model for human lung cancer

Cited by 28 publications

References 26 publications

The effects of combined antioxidant (β‐carotene, α‐tocopherol and ascorbic acid) supplementation on antioxidant capacity, DNA single‐strand breaks and levels of insulin‐like growth factor‐1/IGF‐binding protein 3 in the ferret model of lung cancer

The effects of combined antioxidant (β‐carotene, α‐tocopherol and ascorbic acid) supplementation on antioxidant capacity, DNA single‐strand breaks and levels of insulin‐like growth factor‐1/IGF‐binding protein 3 in the ferret model of lung cancer

Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms

Cigarette Smoke Impairs NK Cell-Dependent Tumor Immune Surveillance

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