Synergism between 2,3,7,8-tetrachlorodibenzo-p-dioxin and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone on lung tumor incidence in mice

Wang, Ying Jan; Chang, Han; Kuo, Yu Chun; Wang, Chia-Woei; Siao, Shih He; Chang, Louis W.; Lin, Pei

doi:10.1016/j.jhazmat.2010.11.082

Cited by 6 publications

(7 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TCDD is regarded as the most potent liver tumor promoter in rodent models [2]. Consistent with this concept, our previous report demonstrated a potential mechanism by which TCDD may act as a lung tumor promoter in an in vivo animal model [15]. In addition, study that used DEN as an initiator and TCDD as a promoter also showed that continuous TCDD exposure is required to promote lung tumorigenesis [1].…”

Section: Discussionmentioning

confidence: 53%

“…For example, male Swiss mice given a single dose of dimethyl-N-nitrosamine (DMN) followed by TCDD for 20 weeks showed an increase in the development of lung alveolar-cell adenomas and carcinomas [14]. Our previous study indicated that TCDD exposure combined with the cigarette smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNK) significantly increased lung tumor formation in A/J mice [15]. These studies indicated the synergistic effects of TCDD in carcinogenesis; however, the underlying mechanisms remain unclear and require further investigation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

TCDD Promotes Lung Tumors via Attenuation of Apoptosis through Activation of the Akt and ERK1/2 Signaling Pathways

et al. 2014

Self Cite

View full text Add to dashboard Cite

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multiple-site, multiple-species carcinogen that induces cancer in multiple organs. The molecular mechanisms underlying TCDD-induced lung tumorigenesis remain unclear. In the present study, a two-stage lung tumorigenesis model was established by administrating a single low dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) combined with TCDD to female A/J mice. The results indicated that TCDD combined with low-dose NNK has a significant tumor-promoting effect compared with TCDD or low-dose NNK alone. Resistance to apoptosis is a hallmark of cancer and is thought to be one of the tumor-promoting mechanisms regulated by TCDD. We performed an additional series of experiments in the normal human bronchial epithelial cell line Beas2B cells, in which TCDD was combined with the apoptosis inducer staurosporine. Our in vitro results confirmed that TCDD could rescue cells from apoptosis induced by staurosporine. The inhibition of apoptosis is likely mediated by the activation of the Akt and ERK1/2 pathways, as determined by the effectiveness of pathway-specific inhibitors in abrogating the anti-apoptotic activity of TCDD. In conclusion, we demonstrated that TCDD promoted NNK-induced lung tumorigenesis and revealed that TCDD inhibits staurosporine-induced apoptosis, at least in part, through the Akt and ERK1/2 signaling pathways.

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

TCDD Promotes Lung Tumors via Attenuation of Apoptosis through Activation of the Akt and ERK1/2 Signaling Pathways

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…was given 3 times a week for an additional 3 weeks (Group 3, 5, 7). The doses of TCDD were modified from those described in published studies, which showed successful enhancement of lung tumorigenesis in mice [6]. To delineate the effects of NNK combined with E2, and/or TCDD in the inflammatory response, we designed a short-term exposure experiment (terminated at the 7 th week after NNK treatment) and a long-term experiment (terminated at the 24 th week after NNK treatment) to evaluate lung tumor induction.…”

Section: Methodsmentioning

confidence: 99%

“…2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a member of the polyhalogenated aromatic hydrocarbon family and is one of the most toxic environmental compounds produced by industrial combustion and chemical manufacturing processes [5]. We have recently reported that the relationship between TCDD exposure and cigarette smoking could be synergistic in the development of lung cancer in female A/J mice [6].…”

Section: Introductionmentioning

confidence: 99%

The Regulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced Lung Tumor Promotion by Estradiol in Female A/J Mice

Chen

Chang

et al. 2014

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Epidemiological studies indicate that women are at a higher risk developing lung cancer than men are. It is suggested that estrogen is one of the most important factors in lung cancer development in females. Additionally, cigarette smoke, and environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play salient roles in female lung carcinogenesis. However, the mechanisms responsible for the interaction of these factors in the promotion of lung cancer are still poorly understood. The present study was designed to explore two ideas: first, the synergistic lung tumorigenic effects of 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNK) combined with TCDD, 17β-estradiol (E2) or both through a long-term treatment experiment, and second, to identify early changes in the inflammatory and signaling pathways through short-term treatment experiments. The results indicate that A/J mice given E2 had strong effects in potentiating NNK-induced activation of MAPK signaling, NFκB, and COX-2 expression. In the long-term exposure model, E2 had a strong tumor promoting effect, whereas TCDD antagonized this effect in A/J mice. We conclude that treatment with NNK combined with either E2 or TCDD induces lung carcinogenesis and the promotion effects could be correlated with lung inflammation. E2 was shown to potentiate NNK-induced inflammation, cell proliferation, thereby leading to lung tumorigenesis.

show abstract

Section: Introductionmentioning

confidence: 99%

The regulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumor promotion by estradiol in female A/J mice

et al. 2013

Self Cite

View full text Add to dashboard Cite

Epidemiological studies indicate that women are at a higher risk developing lung cancer than men are. It is suggested that estrogen is one of the most important factors in lung cancer development in females. Additionally, cigarette smoke, and environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play salient roles in female lung carcinogenesis. However, the mechanisms responsible for the interaction of these factors in the promotion of lung cancer are still poorly understood. The present study was designed to explore two ideas: first, the synergistic lung tumorigenic effects of 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNK) combined with TCDD, 17b-estradiol (E2) or both through a long-term treatment experiment, and second, to identify early changes in the inflammatory and signaling pathways through short-term treatment experiments. The results indicate that A/J mice given E2 had strong effects in potentiating NNK-induced activation of MAPK signaling, NFkB, and COX-2 expression. In the long-term exposure model, E2 had a strong tumor promoting effect, whereas TCDD antagonized this effect in A/J mice. We conclude that treatment with NNK combined with either E2 or TCDD induces lung carcinogenesis and the promotion effects could be correlated with lung inflammation. E2 was shown to potentiate NNK-induced inflammation, cell proliferation, thereby leading to lung tumorigenesis.

show abstract

Synergism between 2,3,7,8-tetrachlorodibenzo-p-dioxin and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone on lung tumor incidence in mice

Cited by 6 publications

References 42 publications

TCDD Promotes Lung Tumors via Attenuation of Apoptosis through Activation of the Akt and ERK1/2 Signaling Pathways

TCDD Promotes Lung Tumors via Attenuation of Apoptosis through Activation of the Akt and ERK1/2 Signaling Pathways

The Regulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced Lung Tumor Promotion by Estradiol in Female A/J Mice

The regulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumor promotion by estradiol in female A/J mice

Contact Info

Product

Resources

About