Indications for nitrosamide formation from the mushroom poison gyromitrin by rat liver microsomes.
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.
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006835:Hydrazones / Q000494:pharmacology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008763:Methylhydrazines / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009002:Monomethylhydrazine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013053:Spectrophotometry
D006835:Hydrazones; D008763:Methylhydrazines; C016577:N-methyl-N-formylhydrazine; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D000079:Acetaldehyde; C005666:gyromitrin; D009002:Monomethylhydrazine; D010634:Phenobarbital