Methylation of rat and mouse DNA by the mushroom poison gyromitrin and its metabolite monomethylhydrazine.
Consumption of false morel (Gyromitra esculenta Fr.) has been associated not only with acute poisoning, but also with a carcinogenic risk. The hydrolysis of acetaldehyde-N-methyl-N-formylhydrazone (gyromitrin, the main toxic component of false morel) results in the formation of the methylating agents N-methyl-N-formylhydrazine (MFH) and N-methylhydrazine (MMH) (by further hydrolysis of MFH). This study reports traces of N-7-methylguanine (N7MeGu) in liver DNA from mice and a rat treated with gyromitrin. After repeated administration of MMH, N7MeGu was identified in rat liver DNA. In mice exposed to MMH according to a dosing scheme identical to that reported to induce tumours in this species, O6-methylguanine was present in liver and kidney DNA. The results indicate that a relatively low carcinogenic risk is associated with false morel consumption. The risk may be greater in individuals with a decreased detoxification rate (acetylation) of MFH, in whom larger amounts of MMH are formed from gyromitrin.
Bergman
K
K
Toxicology Division, National Food Administration, Uppsala, Sweden.
Hellenäs
K E
KE
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism; D000477:Alkylating Agents; D000818:Animals; D002273:Carcinogens; D004249:DNA Damage; D008099:Liver / Q000378:metabolism; D008745:Methylation; D051379:Mice; D009002:Monomethylhydrazine / Q000378:metabolism*; D051381:Rats
D000477:Alkylating Agents; D002273:Carcinogens; D000079:Acetaldehyde; C005666:gyromitrin; D009002:Monomethylhydrazine