Food for Thought

Janet Raloff
Food for Thought

Meat Poses Exaggerated Cancer Risk for Some People

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Last year, the federal government's National Toxicology Program confirmed what many researchers had long been reporting: The heterocyclic amines that form in overcooked meat can trigger colon cancer in animals and probably do the same in people. Now, researchers studying mice have identified a gene that is needed to keep individual animals from becoming especially vulnerable to these carcinogens.

The scientists worked with mice specially bred to lack the gene, which is identical to one sometimes turned off in people. The new findings suggest that such individuals might face an elevated colon cancer risk from overcooked meats.

The good news: A test exists that could identify individuals with such nonfunctioning genes, observes Stephanie Smith-Roe, who reported her team's findings at the Society of Toxicology meeting in San Diego earlier this month. Moreover, the Oregon State University geneticist notes, there are several ways to cook meat that limit formation of these carcinogens—something that would be especially wise for people lacking either of the two genes' activity.

Alphabet soup

At least 17 heterocyclic amines exist. Because of their unwieldy names, most are known by initials, such as PhIP (for 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), IQ (for 2-amino-3-methylimidazo [4,5-f] quinoline), and MeIQx (for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline).

Cells exposed to these agents can develop mutations—damage to their DNA. Because DNA is always under assault from environmental and dietary agents, the body has a host of repair systems to undo the damage or, where that's not possible, to kill cells with damaged DNA. One system called upon to repair DNA that's been done by heterocyclic amines is regulated by genes known as MLH1 and MSH2.

DNA's ladderlike structure is made from two strands of genetic material. Each rung is made from two of the chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Only A should link with T and only G should pair with C. Occasionally, however, as a cell copies its DNA prior to dividing in two, bases in the copied DNA will pair inappropriately—A to C, for instance, or T to G.

Enzymes dispatched by one DNA-repair system search for such so-called mismatch errors. When a mismatch is identified, the enzymes will ordinarily mark the bad patch and initiate its replacement.

Bad copies

However, many individuals possess a malfunctioning MLH1 or MSH2 gene in this mismatch-repair system. Some people are born with a faulty copy of one of those genes, but more often, a gene will become damaged or inappropriately turned off at some point after birth through a process known as hypermethylation. No one knows why hypermethylation occurs, but its gene-disabling effect can be permanent.

People can get by fine with one faulty copy of MLH1 or MSH2 because they normally have a healthy backup copy. However, the good gene copy can also be disabled over time, compromising the mismatch-repair system, the new research shows.

Smith-Roe's team bred mice without functioning copies of the rodent analog of MLH1. At the toxicology meeting, Smith-Roe's group reported what happened to cells in the animals' colons when these rodents were exposed to the heterocyclic amine PhIP.

The chemical gloms onto bases in DNA and makes mismatches much more likely than usual at those points, the researchers report. PhIP usually attaches to a G, which then becomes about as likely to mistakenly pair with an A, a T, or another G.

Unless fixed, such genetic errors can trigger the development of cancer. The researchers found that the genetically altered animals could still correct improper coupling of a G with a T or with another G, but the damaged mismatch-repair system ignored a G-A mispairing.

Compared with normal mice, those bred without the functioning mismatch-repair gene sustained three times as many permanent G-A mismatches in their DNA. The researchers also report that the animals' bodies didn't send the usual signal to kill the damaged cells, a process called apoptosis.

A follow-up study found that mice lacking function of their equivalent to MLH1 were four times as likely to develop precancerous lesions in their colons upon exposure to PhIP as were animals with a functioning gene.

Avoiding heterocyclic amines

Heterocyclic amines form at high temperatures from food constituents such as the simple sugar glucose, the amino acid creatinine, and additional free amino acids, all of which are in meat. Typically, the longer meat cooks at a high temperature, the greater the buildup of the carcinogens. Low-temperature cooking or a quick searing at high temperature won't usually generate the chemicals.

Turning grilled meats frequently so that the heated surface doesn't char is one way to limit the chemicals' formation. Other tactics include adding a little starch to ground meats (see How Carbs Can Make Burgers Safer), marinating meats before cooking (SN: 4/24/99, p. 264: http://www.sciencenews.org/pages/sn_arc99/4_24_99/bob1.htm), and precooking meat in a microwave oven for a few minutes prior to grilling (SN: 4/23/94, p. 264).

Indeed, Smith-Roe notes, meat lovers with a compromised DNA-mismatch-repair system needn't view themselves as facing a cancer sentence. But she advises caution: "Especially with colon cancer, which is such a horrible disease, an ounce of prevention is certainly worth a pound of cure."

Citations

Stephanie Smith-Roe

Dept. of Environmental and Molecular Toxicology

Oregon State University

1007 ALS Building

Corvallis, OR 97331
Further Reading

Raloff, J. 2005. Carcinogens in the diet. Science News Online (Feb. 19). Available at [Go to].

______. 2004. How carbs can make burgers safer. Science News Online (Dec. 4). Available at [Go to].

______. 1999. Well-done research. Science News 155(April 24):264-266. Available at [Go to].

______. 1998. Very hot grills may inflame cancer risks. Science News 154(Nov. 28):341. Available at [Go to].

______. 1996. Another meaty link to cancer. Science News 149(June 8):365.

______. 1994. Meaty carcinogens: A risk to the cook? Science News 146(Aug. 13):103.

______. 1994. Not so hot hot dogs? Science News 145(April 23):264-269.

______. 1994. How cooked meat may inflame the heart. Science News 145(March 12):165.

______. 1994. Sorting out cancer IQs in browned meat. Science News 145(Jan. 8):22.

Seppa, N. 2005. Silenced gene may foretell colon cancer 168(Oct. 1):221. Available to subscribers at [Go to].

______. 2005. Cancer switch: Good gene is shut off in various malignancies. Science News 168(July 16):35. Available at [Go to].

Travis, J. 2004. Code breakers. Science News 165(Feb. 14):106-107. Available to subscribers at [Go to].

Ward, M.H., et al. 1997. Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference. International Journal of Cancer 71(March 28):14-19. Abstract available at [Go to].

Zhang, S., et al. 2001. Msh2 DNA mismatch repair gene deficiency and the food-borne mutagen 2-amino-1-methyl-6-phenolimidazo [4,5-b] pyridine (PhIP) synergistically affect mutagenesis in mouse colon. Oncogene 20(Sept. 20):6066-6072. Abstract available at [Go to].

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