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Hydrocarbon carcinogens induce p53 activity in normal mouse tissue.
1CRC Department of Medical Oncology, Alexander Stone Building, Garscube Estate, Switchback Road, Bearsden, G61 1BD, Glasgow, UK. d.stuart@beatson.gla.ac.uk
Cancer Letters
|October 13, 2001
Summary
Hydrocarbon carcinogens can damage DNA and evade defenses. This study shows "stealth" carcinogens activate p53 transcriptional activity in normal tissues, similar to known agents.
Area of Science:
- Molecular biology
- Toxicology
- Carcinogenesis
Background:
- Certain hydrocarbon carcinogens can damage DNA and bypass cellular defenses.
- The p53 protein is a key regulator of cellular responses to DNA damage.
Purpose of the Study:
- To investigate the ability of hydrocarbon carcinogens to induce p53 transcriptional activity in normal tissues.
- To compare the p53 response to "stealth" carcinogens versus non-stealth agents.
Main Methods:
- Utilized transgenic mice with a LacZ transgene driven by a p53 response element.
- Administered putative stealth carcinogens to assess p53 transcriptional activity in normal tissues.
Main Results:
- Demonstrated that transcriptionally active p53 is induced in normal tissues.
- Showed that this induction occurs in an identical manner following exposure to both stealth and non-stealth carcinogens.
Conclusions:
- Hydrocarbon carcinogens, including "stealth" agents, effectively induce p53 transcriptional activity in normal tissues.
- The cellular defense mechanism involving p53 activation is responsive to a broad range of hydrocarbon carcinogens.