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Your hair - 'a dietary time-clock'
Izelle Theunissen, MRC News
According to PROMEC Unit's Dr Vikash Sewram, your hair is much more than just
your crowning glory. It's also a 'dietary time-clock', giving information about
past exposure to fumonisins.
Fumonisins are mycotoxins produced by the fungus Fusarium verticillioides - a
ubiquitous contaminant of maize. This toxin causes a variety of animal disease
syndromes, including liver cancer in rats. Moreover, epidemiological studies
have shown a correlation between the consumption of fumonisin-contaminated
maize and a high incidence of oesophageal cancer in the Transkei region of the
Eastern Cape, as well as Hebei and Henan provinces in China. Although the
precise role of fumonisins in the context of this disease are still to be
established, there are more than enough reasons for concern. It therefore makes
good sense to assess the levels of human exposure to these fungal toxins.
Fumonisins cause inhibition of a key sphingolipid biosynthetic enzyme (ceramide
synthase) leading to an elevation of the sphingoid base, sphinganine in cells.
This altered sphingolipid biosynthesis potentially provides a useful short-term
biomarker of exposure, which is best expressed as an elevation in the ratio of
sphinganine to the base sphingosine.
This method, however, has its limitations as it is still unclear how sensitive
this approach is with respect to detecting past human exposure. Dr Vikash Sewram
of the MRC's PROMEC Research Unit explains: "We need to ask ourselves, do
all individuals exposed above a certain threshold exhibit an altered ratio, and
specifically, is an altered ratio limited to exposed individuals only. In
addition, the altered ratio is reversible so once exposure to fumonisin stops,
the ratio reverts back to normal, thus making assessment of past exposures not
possible. The normal levels of a control group are also difficult to define
because there is considerable variation in the ratio between individuals and
within an individual over time."
Exposure can also be determined by monitoring the fumonisin levels in the urine
of an individual who is exposed to high levels of the toxin. "But in areas
where contamination levels or maize consumption are relatively low, it would not
be feasible since large volumes of urine would be necessary. In addition, the
time period for detection of fumonisins in urine and blood is very short, so you
can only detect very recent exposures, not past exposures. The rapid elimination
and lack of a major protein and/or DNA adduct makes measurement of fumonisins in
body fluids not feasible as a biomarker for exposure" he says.
Enter hair analysis
In recent years, hair has emerged as a biological specimen for evidence of
chronic drug use in both clinical and forensic investigations. Due to advances
in technology, minute amounts of drugs can be determined. More than a hundred
pharmaceuticals, which include anti-convulsants, anti-depressants and
cardiovascular drugs as well as drugs of abuse (cocaine, opiates and
amphetamines) can be detected in hair.
In addition, while urine analysis can only detect recent exposure, hair analysis
has the potential for greatly expanding the time-window for detection. And it's
far less of a fuss. "Sampling hair is far less intrusive and patients do
not have to endure any pain or discomfort, unlike that generally associated with
the withdrawal of blood. Needles are also no longer necessary, thereby reducing
the danger of blood-borne infections such as HIV and hepatitis," Dr Sewram
says.
So how do the toxins enter the hair? "Once a toxin gets into the
bloodstream, it is transported to the hair by capillaries, which perfuse the
hair root. In this way the toxin is incorporated into the keratinised hair
matrix."
"The toxin can also get into the hair through the endogenous-exogenous
route. This occurs when the toxin is secreted in sweat and sebum on the surface
of the skin, and then re-absorbed into the hair. Once the toxin gets into the
hair, it remains there during the entire growth cycle of the hair shaft. So a
length of hair would indicate to what extent an individual has been exposed to
the toxins over the past months, " says Dr Sewram.
In order to prove this theory, Dr Sewram analysed hair from non-human primates
(monkeys) that had been exposed over a long period to diets containing different
levels of maize cultures of the fungus Fusarium verticilliodes.
"Ultimately, we wanted to determine the extent to which these toxins
accumulate and hence the feasibility of hair analysis as a means of assessing
fumonisin exposure in humans." he says. These results correlated well
between the fumonisin levels in hair and the exposure levels in the monkeys'
diet. In a subsequent study, Dr Sewram exposed rats to a diet containing low
levels of fumonisin and analysed their hair on a weekly basis to determine how
soon after exposure fumonisins would become 'visible' in their hair. This study
was very successful - Dr Sewram presented his findings from both the studies at
the International IUPAC Symposium on Mycotoxins and Phycotoxins in Brazil and
was awarded the International Life Sciences Institute (ILSI) award for the best
oral presentation based on original research.
This research has now been 'translated' for human hair, to determine fumonisin
exposure among the high risk subset of the Transkeian population. "This
means sampling of human hair, and while there are certain cultural barriers to
removing hair, the attitudes of the population towards hair sampling have been
assessed and look quite positive. This area of research has the potential for
further investigation into disease causation mechanisms, especially now that the
actual toxin can be detected," he says.
Despite the positive association between fumonisin exposure and oesophageal
cancer, finding evidence of causality is somewhat of a riddle, due to lack of
protein and/or DNA adducts. "When a toxin enters your system, it can bind
to a protein or nucleic acid. The end result is an adduct formation. There have
been no published reports of fumonisin adducts this far. But now, instead of
looking for adducts, we can trace the actual toxin. It's almost like a
fingerprint for fumonisin exposure," explains Dr Sewram.
"To correlate the maize consumption patterns with the level of fumonisin
exposure remains a major challenge to establish links with human disease. With
the newly developed technique utilising hair, mycotoxin exposure of human
population groups at risk enters a new and exciting phase of human
mycotoxicology."
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