title: The regulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumor promotion by estradiol in female A/J mice.
abstract: 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.
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Rong-Jane
authors.initials: RJ
authors.lastname: Chen
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Chu-Yung
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Visiting Chair Professor of Molecular Medicine, Institute of Molecular Medicine, National Cheng Kung University, Tainan, Taiwan; Visiting Chair Professor, Toxicology Program, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Louis W
authors.initials: LW
authors.lastname: Chang
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Shih-He
authors.initials: SH
authors.lastname: Siao
authors.affiliation: School of Medical Technology and Biotechnology, Taipei Medical University, Taipei, Taiwan; Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
authors.affiliation: Department of Surgery, School of Medicine, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan; Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan; Department of Emergency Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan; Department of Emergency Medicine, Tainan Municipal An-Nan Hospital, China Medical University, Tainan, Taiwan.
authors.forename: Ning-Ping
authors.initials: NP
authors.lastname: Foo
authors.affiliation: Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan Town, Taiwan.
authors.forename: Pinpin
authors.initials: P
authors.lastname: Lin
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Ying-Jan
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009602:Nitrosamines / Q000009:adverse effects*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; D000072317:Polychlorinated Dibenzodioxins; D004958:Estradiol; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone