Investigate the possible role of estradiol in NNK-initiated, TCDD- promoted lung tumorigenesis
碩士 === 國立成功大學 === 環境醫學研究所 === 97 === 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is an ubiquitous environment- al contaminant and highly toxic to several rodent species. During the 20-year period following the Seveso showed TCDD could increase risk of lung cancer, notably among women (RR = 1.3, 95...
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ndltd-TW-097NCKU55200282016-05-04T04:26:09Z http://ndltd.ncl.edu.tw/handle/13310414657843781621 Investigate the possible role of estradiol in NNK-initiated, TCDD- promoted lung tumorigenesis 探討以NNK為起始劑TCDD為腫瘤促進劑所導致的肺腫瘤生成過程中雌素二醇可能之角色 Chu-Yung Chang 張櫸壅 碩士 國立成功大學 環境醫學研究所 97 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is an ubiquitous environment- al contaminant and highly toxic to several rodent species. During the 20-year period following the Seveso showed TCDD could increase risk of lung cancer, notably among women (RR = 1.3, 95% CI: 1.2-4.6). 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 rat. In TCDD studies, hepatic tumor incidence was lower in TCDD-treated ovariectomized (OVX) female rats compared to TCDD-treated sham-operated rats. Thus, we predict that ovarian hormones (estradiol) may be involved in the process of TCDD-induced lung tumorigenesis. The object of this study is to test the hypothesis that whether ovarian hormones (estradiol) is involved in the two-stage lung tumorigenesis promoted by TCDD in female rodent. For this proposal, a two-stage model for lung tumorigenesis sham-operated or OVX- female A/J mice were applied to investigate the effect of ovarian hormones. In in vivo study, OVX- or sham-operated mice were given tumor initiator NNK at week-1 of experiment, received subcutaneous (s.c.) injections of estradiol or corn oil every two days start from week-2 until the end of experiment, given 4 times weekly of TCDD at week-3 and sacrificed at 7 weeks and 24 weeks of experiment. Treatment of female and male mice with NNK alone or combination with TCDD resulted in increased lung tumor incidence compared with female and male control mice. In addition, lung tumor incidence was lower in OVX female mice compared to female mice treated with NNK and TCDD. Whereas, treatment of OVX female mice with NNK and estradiol resulted in a significant increased lung tumor incidence compared with treatment of female mice with combination of NNK, TCDD and estradiol.Hence, TCDD and estradiol both play important role in tumor promotion, nevertheless, inhibition of estradiol promoted tumor incidence by TCDD in NNK-initiated lung tumorigenesis.Short-term mechanistic studies indicated that TCDD and estradiol affect inflammation and cell proliferation by activatin of Mitogen-activated protein kinases (MAPK) pathways and NF-κB pathways at 7 weeks.Thus, we concluded that TCDD and estradiol promote NNK-initiated lung tumorigenesiscould be through enhanced inflammmation and cell proliferation. Ying-Jan Wang 王應然 2009 學位論文 ; thesis 84 zh-TW |
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碩士 === 國立成功大學 === 環境醫學研究所 === 97 === 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is an ubiquitous environment- al contaminant and highly toxic to several rodent species. During the 20-year period following the Seveso showed TCDD could increase risk of lung cancer, notably among women (RR = 1.3, 95% CI: 1.2-4.6). 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 rat. In TCDD studies, hepatic tumor incidence was lower in TCDD-treated ovariectomized (OVX) female rats compared to TCDD-treated sham-operated rats. Thus, we predict that ovarian hormones (estradiol) may be involved in the process of TCDD-induced lung tumorigenesis. The object of this study is to test the hypothesis that whether ovarian hormones (estradiol) is involved in the two-stage lung tumorigenesis promoted by TCDD in female rodent. For this proposal, a two-stage model for lung tumorigenesis sham-operated or OVX- female A/J mice were applied to investigate the effect of ovarian hormones. In in vivo study, OVX- or sham-operated mice were given tumor initiator NNK at week-1 of experiment, received subcutaneous (s.c.) injections of estradiol or corn oil every two days start from week-2 until the end of experiment, given 4 times weekly of TCDD at week-3 and sacrificed at 7 weeks and 24 weeks of experiment. Treatment of female and male mice with NNK alone or combination with TCDD resulted in increased lung tumor incidence compared with female and male control mice. In addition, lung tumor incidence was lower in OVX female mice compared to female mice treated with NNK and TCDD. Whereas, treatment of OVX female mice with NNK and estradiol resulted in a significant increased lung tumor incidence compared with treatment of female mice with combination of NNK, TCDD and estradiol.Hence, TCDD and estradiol both play important role in tumor promotion, nevertheless, inhibition of estradiol promoted tumor incidence by TCDD in NNK-initiated lung tumorigenesis.Short-term mechanistic studies indicated that TCDD and estradiol affect inflammation and cell proliferation by activatin of Mitogen-activated protein kinases (MAPK) pathways and NF-κB pathways at 7 weeks.Thus, we concluded that TCDD and estradiol promote NNK-initiated lung tumorigenesiscould be through enhanced inflammmation and cell proliferation.
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author2 |
Ying-Jan Wang |
author_facet |
Ying-Jan Wang Chu-Yung Chang 張櫸壅 |
author |
Chu-Yung Chang 張櫸壅 |
spellingShingle |
Chu-Yung Chang 張櫸壅 Investigate the possible role of estradiol in NNK-initiated, TCDD- promoted lung tumorigenesis |
author_sort |
Chu-Yung Chang |
title |
Investigate the possible role of estradiol in NNK-initiated, TCDD- promoted lung tumorigenesis |
title_short |
Investigate the possible role of estradiol in NNK-initiated, TCDD- promoted lung tumorigenesis |
title_full |
Investigate the possible role of estradiol in NNK-initiated, TCDD- promoted lung tumorigenesis |
title_fullStr |
Investigate the possible role of estradiol in NNK-initiated, TCDD- promoted lung tumorigenesis |
title_full_unstemmed |
Investigate the possible role of estradiol in NNK-initiated, TCDD- promoted lung tumorigenesis |
title_sort |
investigate the possible role of estradiol in nnk-initiated, tcdd- promoted lung tumorigenesis |
publishDate |
2009 |
url |
http://ndltd.ncl.edu.tw/handle/13310414657843781621 |
work_keys_str_mv |
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