BIOACTIVATION OF MUSHROOM HYDRAZINES TO MUTAGENIC PRODUCTS BY MAMMALIAN AND FUNGAL ENZYMES

Agaritine L-(+)-glutamyl]-4-(hydroxymethylphenyl)hydrazine), the princ ipal hydrazine found in the edible mushroom Agaricus bisporus, as well as the N'-acetyl derivative of 4-(hydroxymethyl)phenylhydrazine and 4 -(hydroxymethyl)benzene diazonium ion, as the tetraborate salt, consid ered as the putative proximate and ultimate carcinogens of agaritine, were all synthesised chemically. The mutagenicity of these compounds a nd of 4-hydrazinobenzoic acid, a precursor of agaritine biosynthesis i n mushroom, was investigated in the Ames test, using Salmonella typhim urium strain TA104, in the absence and in the presence of either mushr oom tyrosinase or rat hepatic cytosol as activation systems. In the ab sence of an activation system the diazonium ion was clearly the most m utagenic of the four compounds studied. When tyrosinase was used as ac tivation system, the mutagenicity of N'-acetyl-4-(hydroxymethyl)phenyl hydrazine was enhanced; glutathione and superoxide dismutase markedly suppressed the mutagenic response. When the mutagenicity of the four c ompounds was evaluated in the presence of rat hepatic cytosol, an incr ease was seen only in the case of N'-acetyl-4-(hydroxymethyl)phenylhyd razine; this was shown to be due to deacetylation releasing the more m utagenic free hydrazine. Collectively, the above data are compatible w ith an activation of agaritine that invokes an initial loss of the gam ma-glutamyl group followed by microsomal oxidation of the free hydrazi ne to generate the diazonium ion. Also of interest is the observation that mushroom tyrosinase can convert N'-acetyl-4-(hydroxymethyl)phenyl hydrazine to mutagenic product(s); whether these products contribute t o the mutagenicity of mushroom extracts remains to be established. (C) 1997 Elsevier Science B.V.