國家衛生研究院 NHRI:Item 3990099045/4709

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Title:	The possible mechanism of TCDD-mediated tumor promotion in NNK-initiated lung tumorigenesis in female A/J mice
Authors:	Lin, PP;Chang, LW;Wang, YJ;Ho, YS
Contributors:	Division of Environmental Health and Occupational Medicine
Abstract:	Introduction:2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a highly persistent trace environmental contaminant and is one of the most potent toxicants known to man. Epidemiological studies have provided suggestive evidence that the risk of lung cancer may be greater in humans exposed to TCDD. In animal studies, TCDD-induced lung lesions appeared to be gender dependent, with predominant increase of the incidence of respiratory tract cancers in female but not in male rats. TCDD is not a mutagen and does not interact with DNA. It is not considered directly genotoxic but is considered a tumor promoter. Two-stage tumorigenesis model applied to investigate the promotion effects of TCDD in lung has seldom been successfully established and reported. The aim of this study was to test the hypothesis that estradiol could be involved in the induction of lung tumors promoted by TCDD in the female rodent.Methods:Two-stage tumorigenesis model was applied to investigate the promotion effects of TCDD in lungs of NNK-initiated A/J mice. The same model was further applied to evaluate the effect of ovarian hormones on indicators of tumor promotion in intact or ovariectomized A/J mice. The following parameters were assessed, including analysis of lung tumor incidence and multiplicity (Histopathology), levels of 8-oxo-dG adducts in urine and lung tissue (GC-MS/MS), CYP1 isozymes activity and expression (EROD assay and immunohistochemistry), and TNF-[alpha] in serum (ELISA).Results:In the current study, we have proved that NNK-initiated A/J mouse is a new model for two-stage lung tumorigenesis assay for TCDD. The combination of NNK and TCDD increased the incidence of lung tumor formation in A/J mice (40%). TCDD alone did not induce lung tumor formation (0%), and only 10% of mice treated with NNK alone developed lung tumor. Ovariectomized A/J mice showed a decreased incidence of lung tumor formation compared to intact mice. The levels of 8-oxo-dG and TNF-[alpha] in tumor bearing mice were significant higher than control group. No significant difference of CYP1A enzyme activity and expression was found in mice lung tissue with different treatment.Discussion and Conclusions:The mechanism for the induction of lung tumors by TCDD in the female rodent is currently unknown. In our previous study, we have demonstrated that TCDD-induced toxicity in human lung cells could be enhanced via interaction between TCDD and estrogen. Herein, we proved, at least in part, that ovarian hormones may play a role in the mechanism of TCDD-induced lung tumorigenesis in rodent.
Date:	2006-11
Relation:	Epidemiology. 2006 Nov;17(6):S319.
Link to:	http://journals.lww.com/epidem/Fulltext/2006/11001/The_Possible_Mechanism_of_TCDD_Mediated_Tumor.841.aspx
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1044-3983&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000241443401370
Appears in Collections:	[Louis W. Chang(1999-2009)] Conference Papers/Meeting Abstract [Pinpin Lin] Conference Papers/Meeting Abstract

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