Effect of the trichothecene mycotoxin diacetoxyscirpenol on nitrosamine-induced oesophageal cancer and on relevant enzymes in oesophagus and liver.
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.
Craddock
V M
VM
MRC Toxicology Unit, Carshalton, Surrey, UK.
D000818:Animals; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives; D004938:Esophageal Neoplasms / Q000139:chemically induced* / Q000201:enzymology; D004947:Esophagus / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D009602:Nitrosamines; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D014255:Trichothecenes / Q000494:pharmacology*
D009602:Nitrosamines; D012717:Sesquiterpenes; D014255:Trichothecenes; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine; C001809:diacetoxyscirpenol