U of G Chemist Hopes to Decode Cancer-Causing Mould
October 19, 2006 - News Release
A University of Guelph chemist is helping to determine how a dangerous mould that forms on wheat and oats causes kidney cancer, which could have an impact on the allowable levels of the substance in Canadian food sources.
Prof. Richard Manderville is studying a type of mycotoxin – a naturally occurring toxin produced from fungi that often attach to grain crops – called ochratoxin A, to see why it causes cancer in animals.
A recent study by Health Canada found that the toxin is present in 50 per cent of Canadian breakfast cereals and many grain products.
“Mycotoxins should be a big, hot item in Canada because ochratoxin A thrives in northern wet climates and is the most potent kidney carcinogen that’s ever been tested by the National Toxicology Program in the United States,” said Manderville.
The problem is, this mould is naturally occurring in grain products and is difficult to prevent, said Manderville. “You can’t see it with the naked eye. The mycotoxins can be detected only because our analytical techniques are so good today. They’ve probably always been in our cereal; we just couldn’t detect them until recently.”
When wheat is processed into cereal or bread, a lot of the mycotoxins are eliminated, but not enough to meet international standards. They resist high temperatures, so cooking also doesn’t destroy them. “Canada produces great wheat, but if we’re not being stringent enough with our allowable levels of mycotoxins, the implications could be huge,” said Manderville.
Scientists currently don’t know how ochratoxin A causes cancer, but he suspects it acts as a genotoxin (something that damages DNA) and, after it’s metabolized, attaches to DNA, initiating a mutation that causes cancer.
Manderville and his research group are the first scientists in the world to assess the nature of DNA damage caused by this toxin. They have found that once ochratoxin A is oxidized, it tends to target the G-base of DNA to form an ochratoxin A DNA adduct. They are now chemically reproducing the adduct to incorporate into DNA using a DNA synthesizer in Manderville’s lab in U of G’s new science complex. He will structurally characterize the modified DNA and, in turn, study repair of the lesion and mutagenicity.
“We’re looking at how this modification alters DNA structure, such as stability of the duplex, and we’re going to determine if it’s mutagenic,” he said. His team is determining if affected DNA gets repaired naturally and, if not, the kinds of mutations that ochratoxin A causes. “Once we know the answers to those questions, that will provide the key for finding out how this molecule causes cancer.”
Currently, the allowable levels of ochratoxin A in food for humans is governed by its toxic properties in pigs. “If we establish that ochratoxin A is a genotoxin, the allowable levels of ochratoxin A in food will be decreased,” said Manderville. “This will be problematic for the food industry because it’s a natural product and they don’t know how to get rid of it.”
He notes that European scientists are working on procedures to prevent the mould from growing on their crops, and European health officials have set stringent regulations on the limits of the toxins in foods.
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