期刊
ENVIRONMENT INTERNATIONAL
卷 128, 期 -, 页码 353-361出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.envint.2019.04.048
关键词
Pancreatic cancer; Cadmium; Carcinogenesis; Risk factors
资金
- Ministry of Education, Science and Technological Development of Serbia [III 46009]
- Oklahoma State University Center for Health Science Pilot Grant Program [1-54333]
Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scarce. Some of established risk factors of PC are connected to an increased cadmium (Cd) body burden. Hence, the aim of this study was to investigate the role of this environmental pollutant in PC development by conducting human observational, experimental and in vitro studies. The case-control study included 31 patients with a histologically based diagnosis of exocrine PC subjected to radical surgical intervention as cases and 29 accidental fatalities or subjects who died of a nonmalignant illness as controls. Animal study included two treated groups of Wistar rats (15 and 30 mg Cd/kg b.w) and untreated control group, sacrificed 24 h after single oral exposure. In in vitro study pancreas hTERT-HPNE and AsPC-1 cells were exposed to different Cd concentrations corresponding to levels measured in human cancerous pancreatic tissue. Cd content in cancer tissue significantly differed from the content in healthy controls. Odds ratio levels for PC development were 2.79 (95% CI 0.91-8.50) and 3.44 (95% CI 1.19-9.95) in the third and fourth quartiles of Cd distribution, respectively. Animal study confirmed Cd deposition in pancreatic tissue. In vitro studies revealed that Cd produces disturbances in intrinsic pathway of apoptotic activity and the elevation in oxidative stress in pancreatic cells. This study presents three different lines of evidence pointing towards Cd as an agent responsible for the development of PC.
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