City of Hope Researchers Identify the Mechanism Used By Cancer-causing Acrylamide to Damage DNA

City of Hope
Tuesday, 6 July 2004

The First Such Study to Use Human Cell Lines

The ability of acrylamide to cause cancer tumor-forming mutations in human and laboratory animal cells is based on the capacity of its primary metabolite, called glycidamide, to bind to DNA, City of Hope Cancer Center researchers report in a study published in the July 7 issue of the Journal of the National Cancer Institute. It is the first acrylamide study to use human cell lines in the laboratory.

Acrylamide, proven to cause cancer in laboratory animals, finds its way into the human diet when amino acids and sugars present in foods are heated at high temperatures during processing, such as frying or roasting. Notable quantities of acrylamide are found in commonly consumed food, such as breakfast cereal, potato chips and French fries, or beverages, such as coffee.

Ahmad Besaratinia, Ph.D., City of Hope research fellow, and Gerd Pfeifer, Ph.D., chair, Division of Biology at City of Hope, conducted the new acrylamide research.

While scientists have long known that administering acrylamide to laboratory animals causes tumor formation in various organs, the exact mechanism involved was unclear.

Basaratinia and Pfeifer in a June 2003 study found that treating mouse cells with acrylamide could cause DNA damage and genetic alterations. They proposed that a reactive metabolite of acrylamide is responsible for its mutation-inducing property, and that it might trigger a multi-stage process leading to tumor formation. Also, they said, the cancer-causing effects of acrylamide in humans remains debatable.

In the new study, Besaratinia and Pfeifer treated human bronchial epithelial cells, a known target cell type for acrylamide-induced tumors, and mouse embryonic fibroblasts with acrylamide and glycidamide. They then mapped the formation of DNA lesions in the human p53 gene, a tumor suppressor gene, and in the cII transgene, which is artificially inserted into the mouse genome.

Besaratinia and Pfeifer found that acrylamide and glycidamide formed identical DNA lesions at similar locations in each gene. But the formation was more pronounced after glycidamide treatment than after acrylamide treatment—and that glycidamide showed a greater capacity to induce genetic alterations in the cII trangene compared to acrylamide.

Earlier this year, two preliminary studies by Swedish scientists suggested that eating food containing acrylamide does not increase the risk of cancers of the colon, rectum or breast.

In their latest study, Beseratinia said, "Despite the ubiquity of acrylamide in the human diet and in the environment—in work settings or in the ambient air, such as a component of environmental tobacco smoke—the profile of human exposure to acrylamide remains very complex."

They conclude that a successful epidemiological study to address the possible link between acrylamide exposure and human cancer will be very challenging and expensive.

For more information, or to contact City of Hope, see their website at: www.cityofhope.org