GENOTOXICITY OF AGARITINE IN THE LACI TRANSGENIC MOUSE MUTATION ASSAY- EVALUATION OF THE HEALTH RISK OF MUSHROOM CONSUMPTION

The mutagenic potency of the common mushroom Agaricus bisporus and cru de agaritine extracted from mushrooms was determined in vivo using a n ew mutagenesis assay with lacI transgenic mice (Big Blue mice). Pairs of female lacI mice were fed one of three diets for 15 wk: (1) fresh m ushrooms 3 days/wk followed by normal lab chow for 4 days/wk; (2) free ze-dried mushrooms mixed at 25% (w/w) into powdered chow; or (3) a mus hroom extract containing 30% agaritine (w/w) mixed into powdered chow. The corresponding daily doses of agaritine were 30 (averaged over the whole week), 80 and 120 mg/kg body weight, respectively. Positive con trol animals received N-nitrosodimethylamine, N-nitrosomethylurea or u rethane, mixed into powdered chow at concentrations corresponding to d aily doses of 0.3, 3 and 130 mg/kg body weight, respectively. DNA of t he forestomach, kidney, liver, lung and glandular stomach of the loci mice was examined for increases in mutant frequency (MF). Control MFs ranged from 5 x 10(-5) to 10 x 10(-5). Positive control substances ind uced a two- to seven-fold increase in MF in their respective target or gans. Of the mushroom diets, significant effects were seen only with t he crude agaritine extract: it induced an increase in MF of 100% in th e kidney and 50% in the forestomach. The other two A, bisporus diets, with lower agaritine doses, showed slightly but not significantly, rai sed MF values in the kidney alone. Thus, agaritine was weakly genotoxi c in vivo; no genotoxic activity other than that attributable to agari tine was detected in A. bisporus. Substances or processes that might i nfluence carcinogenicity by means of non-genotoxic mechanisms (e.g. in crease in fibre, or decrease in calorie intake) are not detected in th e lacl assay. Using a previously derived quantitative correlation betw een mutagenicity in the lacI test and carcinogenic potency, the carcin ogenicity of agaritine in mushrooms was estimated: the average Swiss m ushroom consumption of 4 g/day would be expected to contribute a lifet ime cumulative cancer risk of about two cases per 100,000 lives.