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Craddock VM.
Effect of the trichothecene mycotoxin diacetoxyscirpenol on
nitrosamine-induced oesophageal cancer and on relevant enzymes in oesophagus and
liver.
IARC Sci Publ. 1987;(84):266-9.
MRC Toxicology Unit, Carshalton, Surrey, UK.
To test the concept that human oesophageal cancer is initiated by nitrosamines
and potentiated by consumption of food contaminated by mycotoxins produced by
Fusaria, the effect of the trichothecene mycotoxin diacetoxyscirpenol (DS),
alone and in combination with N-nitroso-N-methylbenzylamine (NMBzA), on rat
oesophagus was studied. Chronic treatment with DS induced oesophageal
hyperplasia, but simultaneous treatment with NMBzA tended to inhibit rather than
to enhance carcinogenesis. The mycotoxin did not inhibit O6-alkylguanine-DNA
alkyltransferase in oesophagus and produced a marked induction of repair protein
in liver. Depletion of the repair protein in oesophagus brought about by
injection of NMBzA was not inhibited by the mycotoxin, and its reappearance was
not delayed. Intubation of DS reduced DNA synthesis in the oesophagus, while
dietary treatment resulted in an increase after nine weeks. The results suggest
that, while simultaneous treatment with DS reduces cancer induced by NMBzA, if
there is first exposure to mycotoxin and induction of hyperplasia, and then
exposure to nitrosamine, so that the carcinogen acts on a vulnerable oesophagus
in which there is an increased rate of cell proliferation, the mycotoxin could
well enhance carcinogenesis.
PMID: 3679383
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