Hepatocarcinogenesis by hydrazine mycotoxins of edible mushrooms

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Abstract
Two edible mushrooms are known to contain hydrazine analogs. The wild false morel Gyromitra esculenta contains up to 0.3% acetaldehyde methylformylhydrazone and N‐methyl‐N‐formylhydrazine (MFH). The latter chemical, under certain conditions, also yields methylhydrazine. The commonly eaten, cultivated mushroom Agaricus bisporus contains up to 0.04% β‐N‐[γ‐L(+)‐glutamyl]‐4‐hydroxymethylphenylhydrazine and 4‐hydroxymethylphenylhydrazine. MFH was administered in drinking water continuously for life to Swiss mice and Syrian (golden) hamsters. In both species the compound induced high incidences of benign and malignant hepatocellular neoplasms. Also, methylhydrazine given orally induced a significant incidence of malignant histiocytomas in the livers of hamsters. The N'‐acetyI derivative of 4‐hydroxymethylphenylhydrazine administered orally to mice gave rise to lung tumors and blood vessel tumors, mainly in the liver. Furthermore, these three compounds produced tumors in various other tissues. Histopathologically, the tumors were classified as benign hepatomas, liver cell carcinomas, angiomas and angiosarcomas of blood vessels, and adenomas and adenocarcinomas of lungs. From representative samples of these neoplasms detailed transmission electron microscopic investigations were also carried out. Since these hydrazine analogs induce tumors in animals and these mushrooms are consumed on a large scale by humans in various parts of the world, their hazardous nature should be considered.