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ID 982

Causes, Diet: Cause

Description:
Meat cooked at high temperatures can produce chemicals that are damaging to cells and DNA.
Transcript:
Cause Meat cooked at high temperatures can produce chemicals that are damaging to cells and DNA. The body has a whole range of enzymes that react with these chemicals to render them inert for eventual disposal. One such enzyme seems to be inactivated in men with prostate cancer. Click the forward arrow or the numbers below to see how the inactivation of this enzyme can lead to prostate cancer development. William Nelson, M.D., Ph.D., Johns Hopkins School of Medicine: “Prostate cancer has become a major scourge for men as they age in the developed world. About 1 in 5, or 1 in 6 men are likely to be diagnosed with prostate cancer in their lifetime.” “The gene that appears to be most commonly inactivated in prostate cells as they become cancerous is a gene that encodes a glutathione-S-transferase enzyme.” “This is an enzyme that can take a chemical scavenger molecule, glutathione, which is typically present at millimolar concentrations inside cells, it can take that scavenger and conjugate it to threatening reactive chemical species whether they be oxidants, reactive oxygen species if you will, or carcinogen-like things.” William Nelson, M.D., Ph.D. is a researcher at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. HIs research focuses on the molecular causes involved in the development of prostate cancer. This has led to the discoveries that inflammation, diet, and gene "silencing" have roles in prostate cancer development. “GSTP1 doesn't seem to be a gene in prostate cancer at least that's controlling growth, invasion, or metastasis or something that you might imagine a classical tumor suppressor gene to do. Rather, it seems to be a gene that controls the vulnerability to further gene damage by reactive oxygen species and carcinogens. So in that sense it acts more like a repair enzyme that is protecting the genome against damage.” “So the GSTP1 gene is inactivated via a mechanism that appears to be very common in most human cancers. It has a gene promoter, a transcriptional promoter region that is a classic CpG island.” “What a CpG island is, is that the nucleotide sequence C followed by G is self-complementary and it's relatively underrepresented overall in the human genome. But often when it's found, it's found clustered into regions of about a kilobase in length.” “When it's clustered in these regions, in most normal genes, the C does not carry a 5-methyl modification.” “We now know that it's also a common mechanism by which genes are turned off in cancer cells. So they carry this region methylated. And GSCP1 is a very classic example of this actually. Its CpG island is quite densely occupied by CpG dinucleotides, and basically in almost every single case both copies of the gene are present and both are methylated.”
Keywords:
sidney kimmel comprehensive cancer center, glutathione s transferase, tumor suppressor gene, gene damage, cancer development, oxygen species, eventual disposal, high temperatures, chemical species
Creative Commons License This work by Cold Spring Harbor Laboratory is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.

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