Acute and chronic effects of diacetoxyscirpenol on cell replication in rat esophagus and stomach.
The effect of the mycotoxin diacetoxyscirpenol (DS) on the upper alimentary tract was studied on account of the association between the consumption of food contaminated by Fusaria and esophageal cancer. Previously it had been shown that a single high dose of DS induced basal cell replication in esophagus and in squamous and glandular stomach. To assess the significance of this effect in relation to the levels of exposure likely to be encountered by man and agricultural animals, it was essential to examine the dose response relationship. Also, the long-term effect of repeated intubations of DS, and of chronic feeding of DS at 10 ppm in the diet, was studied. Intubation of progressively lower doses of DS produced a decreasing effect on replication in esophagus and stomach, but at 0.06 mg/kg replication in squamous and glandular stomach was still more than in the control animals. Intubation repeated weekly for 6-8 weeks produced no detectable change in esophagus or stomach in the surviving animals which were killed at 9 months. When DS was fed in the diet, there was marked hyperplasia in the squamous stomach of two of the four animals which survived for 9 months. These results suggest that DS per se is not carcinogenic for esophagus or for stomach, and that exposure to occasional high doses does not cause persisting abnormalities in replication. However, repeated exposure to high doses would cause repeated periods of hyperplasia, and chronic exposure in some animals could result in continuing hyperplasia. Any increase in replication is likely to promote cancer by increasing the vulnerability of the gastric and esophageal mucosa to carcinogens.
Craddock
V M
VM
MRC Toxicology Unit, Carshalton, Surrey, U.K.
Hill
R J
RJ
Henderson
A R
AR
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D004947:Esophagus / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006965:Hyperplasia; D009183:Mycotoxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000633:toxicity*; D014255:Trichothecenes / Q000633:toxicity*
D009183:Mycotoxins; D012717:Sesquiterpenes; D014255:Trichothecenes; C001809:diacetoxyscirpenol