Document Detail


Genotoxicity of agaritine in the lacI transgenic mouse mutation assay: evaluation of the health risk of mushroom consumption.
MedLine Citation:
PMID:  7737599     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mutagenic potency of the common mushroom Agaricus bisporus and crude agaritine extracted from mushrooms was determined in vivo using a new 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 mushrooms 3 days/wk followed by normal lab chow for 4 days/wk; (2) freeze-dried mushrooms mixed at 25% (w/w) into powdered chow; or (3) a mushroom 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 control animals received N-nitrosodimethylamine, N-nitrosomethylurea or urethane, mixed into powdered chow at concentrations corresponding to daily doses of 0.3, 3 and 130 mg/kg body weight, respectively. DNA of the forestomach, kidney, liver, lung and glandular stomach of the lacI 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 induced a two- to seven-fold increase in MF in their respective target organs. Of the mushroom diets, significant effects were seen only with the crude agaritine extract: it induced an increase in MF of 100% in the kidney and 50% in the forestomach. The other two A. bisporus diets, with lower agaritine doses, showed slightly but not significantly, raised MF values in the kidney alone. Thus, agaritine was weakly genotoxic in vivo; no genotoxic activity other than that attributable to agaritine was detected in A. bisporus. Substances or processes that might influence carcinogenicity by means of non-genotoxic mechanisms (e.g. increase in fibre, or decrease in calorie intake) are not detected in the lacI assay. Using a previously derived quantitative correlation between mutagenicity in the lacI test and carcinogenic potency, the carcinogenicity of agaritine in mushrooms was estimated: the average Swiss mushroom consumption of 4 g/day would be expected to contribute a lifetime cumulative cancer risk of about two cases per 100,000 lives.
Authors:
S E Shephard; D Gunz; C Schlatter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  33     ISSN:  0278-6915     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  1995 Apr 
Date Detail:
Created Date:  1995-06-06     Completed Date:  1995-06-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  257-64     Citation Subset:  IM    
Affiliation:
Swiss Federal Institute of Technology, Schwerzenbach.
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MeSH Terms
Descriptor/Qualifier:
Agaricus
Animals
Bacterial Proteins / genetics
DNA / drug effects,  metabolism
DNA Damage* / genetics
Escherichia coli Proteins*
Female
Food Contamination
Food Handling
Gene Expression Regulation / drug effects,  genetics
Kidney / drug effects,  metabolism
Lac Repressors
Liver / drug effects,  metabolism
Lung / drug effects,  metabolism
Mice
Mice, Transgenic
Mushroom Poisoning / genetics*
Mutagenicity Tests
Mutation / genetics*
Phenylhydrazines / metabolism,  toxicity*
Repressor Proteins / genetics
Risk Factors
Stomach / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Escherichia coli Proteins; 0/Lac Repressors; 0/Phenylhydrazines; 0/Repressor Proteins; 2757-90-6/agaritine; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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