Journal
CANCER RESEARCH
Volume 66, Issue 14, Pages 7143-7150Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-05-4541
Keywords
-
Categories
Ask authors/readers for more resources
Cigarette smoke contains low levels of agonists for the aryl hydrocarbon receptor (AhR; also called the dioxin receptor). However, little is understood about the whole potential of cigarette smoke for activating AhR. In this report, we evaluated the total dioxin-like activity of cigarette smoke using in vitro and in vivo, reporter systems. Cigarette smoke extract (CSE) was prepared front seven cigarette brands (1-20 mg tar content) and subjected to in vitro bioassay based on the xenobiotic-responsive element (XRE) as the sensor and secreted alkaline phosphatase (SEAP) as the reporter. Exposure of reporter cells to CSE triggered activation of XRE in a dose-dependent manner, which was suppressed by functional inhibition of AhR. Direct, brief exposure of the cells to cigarette smoke similarly induced activation of XRE. Using 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) as the standard, the XRE-activating potential (XAP) of individual smoke was evaluated quantitatively. Positive correlation was observed between the tar content and XAP values. The XAP values estimated were extremely high with a range front 18.5 to 51.2 ng 2,3,7,8-TCDD equivalent per cigarette. To further estimate XAP of cigarette smoke in. vivo, we generated transgenic reporter mice that secrete SEAP tinder the control of X-RE. After exposure of the mice to smoke, serum levels of SEAP were significantly elevated within 12 hours, peaked at 24 hours, and declined thereafter. These results evidenced for the first time that cigarette smoke has unexpectedly high dioxin-like potential that triggers the AhR-XRE pathway in vitro and in vivo.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available