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Source: University of Guelph

U of G Chemist Hopes to Decode Cancer-Causing Mould

October 19, 2006

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 Ė a naturally
occurring toxin produced from fungi that often attach to grain crops Ė
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 thatís
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 canít see it with the naked
eye. The mycotoxins can be detected only because our analytical techniques
are so good today. Theyíve probably always been in our cereal; we just
couldnít 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 doesnít destroy them. "Canada produces great
wheat, but if weíre not being stringent enough with our allowable levels of
mycotoxins, the implications could be huge," said Manderville.

Scientists currently donít know how ochratoxin A causes cancer, but he
suspects it acts as a genotoxin (something that damages DNA) and, after itís
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 Mandervilleís lab in U of
Gís new science complex. He will structurally characterize the modified DNA
and, in turn, study repair of the lesion and mutagenicity.

"Weíre looking at how this modification alters DNA structure, such as
stability of the duplex, and weíre going to determine if itís 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 itís a natural product and they donít 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.

Richard Manderville
Department of Chemistry
519 824-4120, Ext. 53963, or

For media questions, contact Communications and Public Affairs: Lori Bona
Hunt, 519-824-4120, Ext. 53338, or Rachelle Cooper, Ext. 56982.



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