0000000000056006
AUTHOR
K. E. Appel
Effect of antibodies against cytochrome P-450 on demethylation and denitrosation of N-nitrosodimethylamine and N-nitrosomethylaniline.
Rat liver microsomes which were induced either with ethanol or PB were incubated with NDMA or NMA. Formaldehyde generation and nitrite formation were measured as metabolic parameters for oxidative bioactivation and denitrosation, respectively. The influence of antiserum PB3a1 and PB22 containing antibodies against the corresponding cytochrome P-450 species on both metabolic functions was investigated. The results showed that the influence on formaldehyde production and denitrosation varied independently in that both parameters were either not affected, or influenced in an opposite way, or inhibited to a different degree. Especially remarkable was the 80% inhibition of formaldehyde generatio…
Effect of potential antidotes on the acute toxicity of acrylonitrile
Rats were intoxicated with lethal doses of acrylonitrile by different routes of application, and the effect of potential antidotes was studied. The cyanide antidotes 4-dimethylaminophenol plus thiosulfate showed some protective effect only after oral but not after i.p. or inhalatory acrylonitrile application. Of the sulfhydryl compounds cysteine, N-acetylcysteine, cysteamine and diethyldithiocarbamate the two antidotes cysteine and, to some lesser extent, N-acetylcysteine proved especially effective. Cysteine, at a dose of 200 mg/kg (i.p.), prevented the lethal effect of 100 mg/kg acrylonitrile (i.p.) even when given 2 h after the acrylonitrile dose. From these experiments a tentative sched…
Irreversible binding of acrylonitrile to nucleic acids
1. [2,3-14C]Acrylonitrile was incubated with rat-liver microsomes, NADPH and either DNA, RNA or bovine serum albumin. Irreversible binding occurred to the macromolecular targets. Binding was lower when incubations were performed without microsomes. 2. Most of the 14C bound to DNA, RNA or polynucleotides (poly-A, poly-C, poly-G, poly-U) after incubation of [2,3-14C]acrylonitrile with rat-liver microsomes and 'conventional' re-isolation of the nucleic acids was removed from the macromolecular target when subsequently chromatographed on hydroxyapatite. 3. Radioactivity attached to DNA after prolonged non-enzymic incubations with [2,3-14C]acrylonitrile was also removed from the DNA by chromatog…