The mutagenic activity of isoniazid, N-acetyl-isoniazid and hydrazine dihydrochloride was investigated in S. typhimurium. Isoniazid was found to possess a weak mutagenic activity only in repair-deficient strains TA1535 and TA100 as well as in the plasmid-containing strain TA92 (10-30 mg/plate) in the Ames test without metabolic activation. Addition of microsomal enzymes by S9 mix decreased this direct mutagenic activity. In contrast, preincubation of isoniazid with crude liver homogenate from mice, rats or Syrian golden hamsters for 4 h prior to plating with bacteria liberated a mutagenic compound which is equally active in both repair-deficient and repair wild-type strains (0.5-5 mg/plate). This activation pathway is independent of NADPH, is heat-sensitive and is operative only in a total liver homogenate in suspension. The highest capacity for mutagenic activation was achieved with liver homogenate from hamsters, followed by that from mice and rats. Furthermore, this mutagenic activation is paralleled by formation of hydrazine, as demonstrated in colorimetric measurements with p-dimethylaminobenzaldehyde. N-Acetyl-isoniazid is without mutagenic activity under similar conditions, and liberation of hydrazine was never detected. This means that, besides having a weak direct genetic activity, isoniazid is a promutagen, and formation of hydrazine is the first step in metabolic activation. It is concluded that the genotoxic properties of isoniazid in mammals are primarily determined by the pharmacokinetic behavior of the ultimate reactive metabolite. This result must be taken into consideration in risk assessment performed for mutagenic and carcinogenic properties of isoniazid in man.

Animals↗

PubMedDate not supplied

Bacterial mutagenicity of the tranquilizing constituents of Valerianaceae roots.

The valepotriates valtrate/isovaltrate and dihydrovaltrate are considered to be the main tranquilizing constituents of drugs derived from the roots of several Valerianaceae. The decomposition products of valtrate and isovaltrate include the metabolites baldrinal and homobaldrinal, respectively, whereas the decomposition products of dihydrovaltrate do not include baldrinal-like metabolites. Purified valtrate/isovaltrate, dihydrovaltrate, baldrinal and homobaldrinal were investigated for their genotoxic activity in the Salmonella/microsome test and the SOS-chromotest. The valepotriates developed mutagenic activity in these test systems only in the presence of S9 mix, whereas both baldrinals showed mutagenic effects in both tests with and without metabolic activation.

Animals↗

PubMedDate not supplied

Codigestion of proteinaceous industrial waste.

Organic wastes are increasingly collected source separated, thus requiring additional treatment or recovery capacities for municipal biowastes, organic industrial wastes, as well as agroindustrial byproducts. In this study, we demonstrate that anaerobic digestion is preferentially suited for highwater- containing liquid or pasty waste materials. We also evaluate the suitability of various organic wastes and byproducts as substrates for anaerobic digestion and provide a current status survey of codigestion. Biodegradation tests and estimations of the biogas yield were carried out with semisolid and pasty proteins and lipids containing byproducts from slaughterhouses; pharmaceutical, food, and beverage industries; distilleries; and municipal biowastes. Biogas yields in batch tests ranged from 0.3 to 1.36 L/g of volatile solidsadded. In continuous fermentation tests, hydraulic retention times (HRTs) between 12 and 60 d, at a fermentation temperature of 35 degrees C, were required for stable operation and maximum gas yield. Laboratory experiments were scaled up to full-scale codigestion trials in municipal and agricultural digestion plants. Up to 30% cosubstrate addition was investigated, using municipal sewage sludge as well as cattle manure as basic substrate. Depending on addition rate and cosubstrate composition, the digester biogas productivity could be increased by 80-400%. About 5-15% cosubstrate addition proved to be best suited, without causing any detrimental effects on the digestion process or on the further use of the digestate.

Bacteria, Anaerobic↗

PubMedDate not supplied

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.

Acetaldehyde↗