Indications for nitrosamide formation from the mushroom poison gyromitrin by rat liver microsomes

Abstract

1. N-Methyl-N-formylhydrazine, formed by hydrolysis from gyromitrin, the main toxin of the edible mushroom Gyromitra esculenta, lowers the cytochrome P-450 concn. in liver microsomes after its application to rats.

2. This decrease can be intensified by pretreatment of the rats with phenobarbital but not by induction with 3-methylcholanthrene.

3. The effect of methylformylhydrazine can be abolished in relation to inhibitor-treated controls by prior administration of SKF 525-A but not metyrapone.

4. After addition of methylformylhydrazine to liver microsomes of rats pretreated with phenobarbital in the presence of a NADPH-regenerating system and O₂ a metabolite was formed with a time dependent difference spectral max. at 425 nm. When subsequently the microsomal mixture was reduced by addition of NADPH or sodium dithionite, a new spectrum was obtained with a max. at 447 nm, which decreased within a few minutes with a slight blue-shift.

5. The cytochrome P-450 mediated oxidation of methylformylhydrazine to a hydroxylamine derivative and further to a nitrosamide, is discussed in relation to its importance for the biological action of the hydrazine. This nitrosamide formation may be the reason for the known hepatocarcinogenicity of methylformylhydrazine.