کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2598599 1562632 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lasting glycolytic stress governs susceptibility to urethane-induced lung carcinogenesis in vivo and in vitro
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Lasting glycolytic stress governs susceptibility to urethane-induced lung carcinogenesis in vivo and in vitro
چکیده انگلیسی


• The mouse strains have different susceptibility to lung carcinogenesis.
• Urethane-induced lung carcinogenesis is associated with glycolytic stress.
• Lasting glycolysis removes difference of susceptibility to lung carcinogenesis.
• Glycolytic metabolism is a direct initiator of tumorigenesis.
• 10× injection of urethane is a valuable model for studying lung carcinogenesis.

Urethane is a recognized genotoxic carcinogen in fermented foods and beverages. This study is to compare susceptibility of ICR mice, BALB/c mice and C57BL/6 mice to urethane-induced lung carcinogenesis. The mice were injected intraperitoneally with 600 mg/kg of urethane for three times or ten times at 7-day intervals. At week 26, lung carcinogenic incidence was found in 40% ICR mice, 20% BALB/c mice and 10% C57BL/6 mice of the 3× injection group, respectively, whereas 100% lung tumor incidence took place in three mouse strains of the 10× injection group. In the 10× injection group, urethane induced lasting glycolytic stress of lung with an increase in lactate, monocarboxylate transporter 1 (MCT-1), reactive oxygen species(ROS) and 7,8-dihydro-8-oxo-29-deoxyguanosine (8-OHdG) and a decrease in pyruvate dehydrogenase (PDH) and cytochrome C oxidase (COX). In the 3× injection group, urethane also promoted lung glycolytic stress at the end of urethane injection but it lasted no more than 7 days besides in lung tumor-bearing mice. Metformin as a glycolytic enhancer promoted urethane carcinogenic efficacy in the 3× injection group, whereas 2-deoxy-glucose (2-DG) as a glycolytic inhibitor decreased urethane carcinogenic efficacy in the 10× injection group. Further, urethane promoted tumor survival in A549 cells by inducing cancer stem-like cellular state. These data suggest that lasting glycolytic stress is sufficient for urethane-induced lung tumorigenesis, and that urethane 10× injection-induced lung cancer can serve as a valuable model for lung tumor biology and tumor prevention.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 240, Issue 1, 5 January 2016, Pages 130–139
نویسندگان
, , , , , , , , , ,