Stimulation of DNA replication in rat esophagus and stomach by the trichothecene mycotoxin diacetoxyscirpenol.
Consumption by man of cereals contaminated by high levels of Fusaria mycotoxins has caused alimentary toxic aleukia, while chronic consumption at lower levels of contamination has been implicated in esophageal cancer in China and South Africa. Dietary treatment of animals with extracts of Fusaria cultures or with the trichothecene diacetoxyscirpenol (DS) caused esophageal hyperplasia but not cancer. The explanation could be that esophageal cancer is initiated by other factors, possibly by nitrosamines, and that Fusaria mycotoxins act either as co-carcinogens or as promoters as a result of their ability to stimulate cell replication. The effect of DS on replication in esophagus was therefore studied. As squamous stomach has a very similar histological structure to esophagus, the effect of DS on stomach was studied also. A high dose of DS given by gavage was shown by the bromodeoxyuridine-antibody technique to increase DNA replication in the basal cells of the esophagus and of the squamous and glandular stomach. For stomach, this correlated with an increased incorporation of tritiated thymidine into DNA, and an increase in ornithine decarboxylase activity. These effects had returned to normal by 7 days. The increased replication was apparently not a result of cell damage and restorative hyperplasia. It is suggested that, as has been proposed recently for butylated hydroxyanisole, DS may enhance carcinogenesis when exposure is sufficient to stimulate cell replication. This contrasts with the non-threshold action of initiating carcinogens. For man, acute exposure to the critical dose of DS probably occurs only under exceptional circumstances, as during outbreaks of alimentary toxic aleukia. Prolonged exposure to lower dose levels is more likely to be relevant.
MRC Toxicology Unit, Carshalton, Surrey (U.K.).
V M
VM
Craddock
R J
RJ
Hill
A R
AR
Henderson
D000818:Animals; D004261:DNA Replication / Q000187:drug effects*; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D009183:Mycotoxins / Q000633:toxicity*; D009955:Ornithine Decarboxylase / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000633:toxicity*; D013270:Stomach / Q000187:drug effects*; D014255:Trichothecenes / Q000633:toxicity*
D009183:Mycotoxins; D012717:Sesquiterpenes; D014255:Trichothecenes; D009955:Ornithine Decarboxylase; C001809:diacetoxyscirpenol