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J Lüthy

Publications and source records attributed to J Lüthy.

At least 55 records · Page 3Linked to original sources
PubMed1986

The mutagenic activity of agaritine--a constituent of the cultivated mushroom Agaricus bisporus--and its derivatives detected with the Salmonella/mammalian microsome assay (Ames Test).

Purified agaritine (N'-(gamma-L(+)-glutamyl)-p-hydroxymethylphenylhydrazine) isolated from Agaricus bisporus, p-hydrazinobenzoic acid (its presumptive precursor) and some agaritine-degradation products were tested for mutagenic activity with the Salmonella/mammalian microsome assay (Ames test). Consistent with the literature, agaritine showed a distinct direct-acting mutagenicity with the strain TA1537 (30 revertants/mumol) and with TA97. Incubation of agaritine at alkaline pH increased the mutagenic effect. Pre-incubation of agaritine with gamma-glutamyl transferase (GT) during 10 h at room temperature (pH 8.2) even enhanced the mutagenicity by a factor of 8 to 16 depending on the strain. In accordance with this finding, synthetic p-hydroxymethylphenylhydrazine (the presumptive product of the GT catalyzed degradation) showed also a distinct direct-acting mutagenicity, but the increase was only about 3- to 6- times compared with agaritine. The hypothetical ultimate mutagenic metabolite of agaritine, the p-hydroxymethylbenzenediazonium ion, a compound occurring naturally in A. bisporus, showed the highest mutagenic activity (with TA1537 approximately 300 to 1,000 revertants/mumol).

Agaricales↗
PubMed1985

[The occurrence of goitrogenic substances in milk. 1. Release of goitrin in the milk of cows fed on rapeseed extract cakes].

A total of six cows, divided into 3 groups, were fed various amounts of rape cake containing 6 g of goitrin/kg over a period of 7 days. The cows were milked twice a day and the goitrin content of the heated milk samples were determined by a HPLC-method within 2 h. When rape cake was fed at 0.39, 1.9 and 3.9% resp. of the total feed this resulted in medium goitrin values of 37, 163 and 707 micrograms/l milk. These values correspond to a transfer of about 0.1% of the original progoitrin content in the feed. 12 h after the last rape feeding the amount of goitrin in the milk was below the detection limit of 7 ppb. The toxicological significance of these findings are dicussed.

Animal Feed↗
PubMed1985

In vivo covalent binding of retronecine-labelled [3H]seneciphylline and [3H]senecionine to DNA of rat liver, lung and kidney.

Retronecine-labelled [3H]seneciphylline ([3H]SPH) and [3H]senecionine ([3H]SON) of high specific radioactivity (22 and 49 mCi/mmol, respectively) were prepared biosynthetically with seedlings of Senecio vulgaris L. using [2,3-3H]putrescine as precursor. [2,3-3H]Putrescine was synthesized by Gabriel synthesis of 1,4-diamino-2-butene from 1,4-dibromo-2-butene and catalytic hydrogenation of the product with tritium gas. Rats of both sexes were treated with the labelled pyrrolizidine alkaloids (PAs) (75-215 microCi SPH or 40-485 microCi SON/kg body wt.) and killed after 6 h or 4-5 days. SON-treated females excreted 83.4 +/- 0.2% of applied radioactivity in faeces and urine within 4 days whereas equally treated males excreted 90.9 +/- 3.2% in the same time. Excretion of 3H-activity from SPH-treated females was completed within 5 days (104.7 +/- 6.4%). Corresponding with these results, tissue levels were highest in SON-treated females. DNA and proteins were isolated from liver, lungs and kidneys and covalent binding of the alkaloids to DNA was determined. A Covalent Binding Index (CBI, mumol alkaloid bound per mol nucleotides/mmol alkaloid administered per kg body wt.) of 210 +/- 12 was found for the liver from SON-treated females whereas binding to liver DNA of males was lower by a factor of 4. The DNA damage determined six hours after treatment persisted during the following 4 days. Administration of [3H]SPH to female and male rats resulted in a CBI of 69 +/- 7 and 73/92, respectively, for the liver DNA. Furthermore we found binding of both alkaloids to DNA of lungs and kidneys in male and female rats. The in vivo formation of [3H]SON derived DNA adducts could be proved by HPLC analysis of hydrolyzed DNA.

Animals↗
PubMed1984

Goitrin--a nitrosatable constitutent of plant foodstuffs.

N-nitrosamides are known as direct-acting carcinogens at the site of their formation; they do not need any metabolic activation in vivo. The conditions leading to their formation in the stomach, and also their genotoxicity, have been thoroughly studied with some model compounds. Several reports link this type of compound to the induction of gastric cancer in human. However, only limited data are presently available about possible precursors of N-nitrosamides in foods. In the present study we found that goitrin --a naturally occurring compound in cruciferous vegetables and rape--could be easily nitrosated by treatment with nitrite under stomach conditions, yielding with loss of sulfur the N-nitroso- oxazolidone 4 (fig.). This product has a mutagenicity pattern and potency similar to that of N-nitroso-N-methyl-N'- nitroguanidine (MNNG) in the Ames Salmonella/mammalian microsome test.

Biotransformation↗
PubMed1984

[Rapid determination of agaritin in commercial mushrooms (Agaricus bisporus) with high performance liquid chromatography].

A procedure is described for the determination of agaritine in the commercial mushroom Agaricus bisporus by high performance liquid chromatography (HPLC). Agaritine was extracted from the mushroom sample with methanol and the filtered extract diluted with phosphate buffer. An aliquot of this solution was used directly for the HPLC-separation on a cation exchange column (Partisil SCX) with 0.5 mM phosphate buffer (pH 1.8) as mobile phase and u.v. monitoring at 237 nm. The agaritine content in fresh mushrooms was found to be in the range of 94-629 mg/kg fresh weight. Canned mushrooms contained 1-55 mg/kg drained weight with 3-103 mg/l in the liquid. The highest agaritine values were found in dried commercial mushrooms amounting to 2,110-6,905 mg/kg.

Basidiomycota↗
PubMed1984

[Mutagenicity testing of commercially used strains of P. camemberti and P. roqueforti].

We tested the mutagenic potential of crude extracts of 18 strains of Penicillium camemberti and 6 strains of P. roqueforti, which are used commercially in the production of mould ripened cheese in Switzerland. No mutagenic activity could be detected in any of the extracts. Roquefortine, a mycotoxin of P. roqueforti, often found in Blue cheese, was negative in the Amestest. The results obtained do not lead reasons for experting undesired long term effects from the consumption of mould ripened cheese.

Animals↗
PubMed1984

[Subchronic toxicity testing of mold-ripened cheese].

The biological effects of known mycotoxins of Penicillium roqueforti or P. camemberti and other still unknown, but potentially toxic metabolites in mould ripened cheese (commercial samples of Blue- and Camembert cheese) were investigated. High amounts of mycelium (equivalents of 100 kg cheese/man and day) were fed to mice in a subchronic feeding trial. The following parameters were determined: development of body weight, organ weights, hematology, blood plasma enzymes. No signs of adverse effects produced by cheese mycotoxins could be detected after 28 days. No still unknown toxic metabolites could be demonstrated. From these results no health hazard from the consumption of mould ripened cheese, even in high amounts, appears to exist.

Animals↗
PubMed1984

Mutagenic activity of the pyrrolizidine alkaloids seneciphylline and senkirkine in Drosophila and their transfer into rat milk.

Seneciphylline and senkirkine, two pyrrolizidine alkaloids that occur in animal feeds and medicinal herbs, respectively, have been tested for their ability to produce sex-linked recessive lethals in males of Drosophila melanogaster using the Basc test (3-day feeding method). Seneciphylline was found to be mutagenic at concentrations of 10(-5), 10(-4) and 10(-3)M, which produced 3.8% sex-linked recessive lethals (983 chromosomes tested). 9.0% (708) and 15.3% (327), respectively. Senkirkine (10(-5)M) produced 4.4% sex-linked recessive lethals (2541 chromosomes tested) against 0.17% (9081) in controls. Brood pattern analysis with senkirkine showed maximum sensitivity in the late spermatid stage of spermatogenesis, which agrees with evidence that pyrrolizidine alkaloids act as indirect mutagens. Flies fed with milk from lactating rats given an oral dose of 25 mg seneciphylline/kg showed 1.2% sex-linked recessive lethals (1477 chromosomes tested), against 0.3% (1533) in controls.

Animals↗
PubMed1984

Metabolism and distribution of 3,4-epithiobutanenitrile in the rat.

The metabolism and distribution of [2-14C]- and 35S-labelled 3,4-epithiobutanenitrile (4ETN), a thiirane occurring naturally in cruciferous vegetables, was studied in the rat. A dose of c. 11 mg 4ETN/kg body weight was rapidly transformed into water-soluble compounds and was mainly excreted in the urine, irrespective of the route of administration (oral or ip). The main metabolite in the urine was identified by gas chromatography-mass spectrometry as a mercapturic acid derivative. Low residual radioactivity demonstrated in organs 72 hr after administration was consistent with an earlier report that the thiirane may function as a weak biological alkylating agent.

Animals↗
PubMed1983

[Biogenic amines in food: effects of histamine, tyramine and phenylethylamine in the human].

The effect of 25 mg histamine, 25 mg tyramine and 5 mg phenylethylamine resp. in apple juice on 27 healthy volunteers was studied using a randomized placebo-controlled double-blind procedure. No statistically significant effect was found with histamine and tyramine, but phenylethylamine produced symptoms like headache, dizziness and discomfort in some volunteers. In a second experiment the effect of four different wines (2 dl) containing naturally several biogenic amines in various amounts (histamine n.d. - 21 ppm; tyramine 1-23 ppm; phenylethylamine n.d. - 6 ppm; putrescine 2-55 ppm) on 20 volunteers was recorded. The percentage of volunteers experiencing symptoms was of the same order of magnitude as in the first experiment. No correlation was found to exist in this second experiment between the occurrence of symptoms and the concentration of biogenic amines in the wine samples.

Beverages↗
PubMed1983

Transfer of [3H]pyrrolizidine alkaloids from Senecio vulgaris L. and metabolites into rat milk and tissues.

[3H]Retronecine and [3H]necic acid-labelled senecionine and seneciphylline were prepared biosynthetically with seedlings of Senecio vulgaris L. using [2,3-3H]putrescine and [4,5-3H]isoleucine, respectively, as precursors. Lactating rats dosed with these differently labelled pyrrolizidine alkaloids (PAs) excreted within 3 h approx. 0.08% of the applied radioactivity in the milk mainly as yet not identified water-soluble retronecine-derived metabolites and with approx. 0.02% as unchanged PAs. Highest tissue levels of PAs and metabolites, 6 h after administration, were found in liver and lungs.

Animals↗
PubMed1982

Pyrrolizidine alkaloids from Symphytum officinale L. and their percutaneous absorption in rats.

An analysis of a commercial sample of Symphyti radix originating from Poland with a total alkaloid content of 0.07% revealed the presence of 7 pyrrolizidine alkaloid-N-oxides: 7-acetyl intermedine, 7-acetyl lycopsamine as the main constituents and lycopsamine, intermedine, symphytine and traces of 2 further not yet identified alkaloids. The percutaneous absorption of these alkaloids was investigated in rats, using a crude alcoholic extract of the plant corresponding to a dose of 194 mg alkaloid-N-oxides/kg b.wt. The excretion of N-oxides in the urine during 2 days was in the range of 0.1-0.4% of the dose. The dermally absorbed N-oxides are not or only to a small extent converted to the free alkaloids in the organism. The oral application led to a 20-50 times higher excretion of N-oxides and free alkaloids in the urine.

Animals↗
PubMed1980

In vivo covalent binding of aflatoxin B1 and aflatoxin M1 to liver DNA of rat, mouse and pig.

[14C]Aflatoxin B1 (AFB1) was isolated from cultures of Aspergillus parasiticus grown on [1-14C]sodium acetate. Covalent binding of AFB1 to liver DNA of rat and mouse was determined 6-8 h after oral administration. The effectiveness of covalent binding, expressed as DNA binding per dose in the units of a 'Covalent Binding Index' (CBI), (micromol aflatoxin/mol DNA nucleotides)/(mmol aflatoxin/kg animal), was found to be 10 400 for rats and 240 for mice. These CBI partly explain the different susceptibility of the two species for the incidence of hepatic tumors. The corresponding values for pig liver DNA, 24 and 48 h after oral administration, were found to be as high as 19 100 and 13 300. DNA-binding has not so far been reported for this species although it could represent an appropriate animal model for studies where a human-like gastrointestinal tract physiology is desirable. Aflatoxin M1 (AFM1) is a metabolite found in the milk of cows that have been fed AFB1-contaminated diet. [14C]AFM1 was also found to be produced by cultures of A. parasiticus giving a yield of about 0.3% of the total aflatoxins. A test for covalent binding to rat liver DNA revealed a CBI of 2100 showing that AFM1 must also be regarded as a strong hepatocarcinogen. It is concluded that AFB1 contaminations should be avoided in dairy feed.

Aflatoxin B1↗