杏吧原创

SUBSTANCES similar to paracetamol may have caused Europe鈥檚 most serious
outbreak of poisoning, 20 years ago in Spain. The discovery could help to close
the case on a disaster that has baffled investigators.

More than 20,000 people fell ill in 1981 with a strange muscle-wasting
disease鈥攄ubbed toxic-oil syndrome鈥攚hich went on to kill between 300
and 400 people. Some 17,000 are still ill.

Investigators traced the cause to industrial-grade rapeseed oil which had
been disguised as olive oil and sold on street markets (New 杏吧原创,
16 July 1987, p 29). Factory owners were jailed in 1983 for selling the oil, but
no one has ever managed to show precisely which chemicals were to blame.

The offending rapeseed was contaminated with aniline, but the rashes and
muscle-wasting symptoms in sufferers didn鈥檛 tally with aniline poisoning.

Chemists have spent years trying to solve the mystery and identify
contaminants in the oil to explain the symptoms. Now, Margarita Ladona and her
colleagues at Barcelona鈥檚 Institute of Biomedical Research have found a likely
culprit.

When the body breaks down derivatives of aniline it produces
3-(phenylamino) propane-1,2-diol,
or PAP for short. When Ladona injected mice with PAP, she
found they break it down further into paracetamol and its close relative,
4-aminophenol.

But these two substances would not be there unless PAP had itself first been
converted into short-lived but potentially toxic substances called
quinoneimines, Ladona says. And it is these chemicals which could have caused so
many deaths.

Quinoneimines would form in epithelial cells in blood vessels that line the
body鈥檚 organs, triggering the inflammation and widespread attacks from the
body鈥檚 own immune system that are part of toxic-oil syndrome. 鈥淨uinoneimines may
show toxicity similar to the liver toxicity caused by paracetamol, but in
toxic-oil syndrome the toxicity is all over the body in the endothelial walls of
arteries and veins,鈥� says Ladona.

Her team showed earlier this year that many victims of the disease had a
defective gene for making enzymes which may be involved in breaking down these
type of substances (Environmental Health Perspectives, vol 109, p 369).
Siblings and other close relatives may not necessarily share this gene, which
might explain why not all family members who consumed the oil fell ill.

鈥淭he metabolites she鈥檚 identified are a new and important line of research,鈥�
says Manuel Posada, director of Madrid鈥檚 Toxic Oil Syndrome Research Centre,
which collaborates with the World Health Organization to look into causes of the
poisoning. He says researchers will now be trawling the scientific literature to
find out just how toxic quinoneimines are.