February 12, 2010

Study weighs diet’s impact on colon tumor formation

Featured Image

Aramandla Ramesh, Ph.D., second from left, works in his Meharry Medical College lab with, from left, doctoral candidates Jeremy Myers and Deacqunita Harris and graduate student Ashley Huderson. (photo by Joe Howell)

Study weighs diet’s impact on colon tumor formation

For nearly 15 years, Aramandla Ramesh, Ph.D., assistant professor of Biochemistry and Cancer Biology at Meharry Medical College, has studied environmental toxins and how they impact health.

His most recent study investigated whether the formation of tumors in the colon of mice was the result of the presence of toxic chemicals and type of fat in the diet. The paper, published recently in Toxicologic Pathology, was co-authored by Meharry graduate student Deacqunita Harris and Vanderbilt University Medical Center researchers Mary Kay Washington, M.D., and L. Jackson Roberts II, M.D.

Initial funding for his work came from a grant from the Advanced Research Cooperation in Environmental Health (ARCH) Consortium, a collaborative effort of the Meharry-Vanderbilt Alliance.

But Ramesh's research on the environmental factors that lead to colon cancer recently received a boost — a nearly $1 million grant from the National Cancer Institute for the next four years.

“With this funding, I will be able to extend my study to see what kind of mechanisms exist in the body to process toxicants that are triggered by different kinds of fat in the diet that would accelerate the development of colon cancer,” said Ramesh.

“For example, when people eat grilled food, during the process there are lots of chemicals generated because of the heat. The chemicals are in the grease and the fat. We want to know what kind of molecular changes occur in the body and find the mechanism by which this dietary fat modulates hydrocarbon-induced colon cancer.

“Although we use genetically engineered mice and examine what kinds of changes occur in the colon, our hope is to validate our findings in population-based controlled studies.”

Ramesh and colleagues were able to target the compounds called benzo(a)pyrene, which is a hydrocarbon and environmental toxin that is a byproduct of industrial emissions, automobile exhaust, chemicals generated by cooking red meat at high temperatures and cigarette smoke.

The extra funding will allow Ramesh to further examine whether the type of fat — unsaturated or saturated — increases the chance for tumor development in the colon.

What he has discovered is that mice given unsaturated fat, like corn oil and peanut oil, along with the toxic chemicals develop small tumors. Mice given saturated fats like coconut and palm oil or lard, which remain in the body for longer periods of time, in concert with the toxic chemicals led to larger tumors.

“As part of the grant, I will collaborate with Vanderbilt as we survey colon cancer patients,” said Ramesh. “We want to know their diets and family history. We know that 70 percent of colorectal cancers come from environmental and lifestyle factors.”

Darryl Hood, Ph.D., ARCH program director at Meharry Medical College and a co-author on the first paper, said Ramesh's work is the foundation for a new school of thought in terms of the mechanisms that contribute to benzo(a)pyrne-induced toxicity.

“Dr. Ramesh has served as the impetus for the expansion of the toxicology programs at Meharry,” said Hood, professor of Neuroscience and Pharmacology at Meharry. “Some of the work he is doing will potentially lead to therapeutic options.”

Michael Aschner, Ph.D., Gray E.B. Stahlman Professor of Neuroscience, serves as the principal investigator for the ARCH grant at VUMC.

“The work Dr. Ramesh is doing will have translational value in better understanding how diet affects colon cancer development in humans exposed to these compounds,” said Aschner, also professor of Pediatrics and Pharmacology.

“This is the first time I know of where information is derived on how dietary intake is correlated with tumor development in relationship to the exposure to the compounds.”

Ramesh's research fits into the vision and mission of Meharry as well as the Alliance's focus of eliminating cancer disparities, which is a National Cancer Institute-funded program headed by Samuel Adunyah, M.D., chair of Cancer Biology at Meharry, and Harold Moses, M.D., director emeritus of Vanderbilt-Ingram Cancer Center.

“Most of the people from the African-American community are disproportionately impacted by colorectal cancer, and environmental influences are to blame for this,” said Ramesh.