sodium-nitrite and dodine

The pollution of the environment with pesticides of different chemical classes (amines, carbamates, guanidines, etc.) and nitrogen fertilizers creates the danger of the in vivo formation of carcinogenic nitrosocompounds. The fungicide Dodin represents dodecylguanidineacetate (DGA), whose chemical structure presupposes a possibility for nitrosofication in the presence of nitrites. The experiments were carried out on albino rats in which 1/10 LD50 sodium nitrite and DGA were introduced orally and in combination. On the 1st, 2nd, 4th, 8th, 15th and 30th days after the onset of the effect we determined the activity of the oxidases with mixed function (OMF) at two levels of biological organization: at the level of intact organism after loading with aminopyrine (AP) and subsequent determination of its basic metabolites in the urine; at subcellular level (microsomal liver fraction) - by the velocity of N-demethylation of AP, hydroxylation of aniline and by the cytochrome P-450 content. The independent action of sodium nitrite leads to a slight inhibition of OMF at subcellular level (28--34%) only after a single treatment. DGA does not change the activity of OMF. The combined action of the two agents causes considerable OMF inhibition (63--67 per cent) on the 1st, 2nd, 4th and 15th days at both levels. The concentration of microsomal protein decreases parallel to OMF inhibition. The data obtained suggest that a new compound is formed under the conditions of the experiment, probably through in vivo nitrosification of the pesticide. This is also testified by the established qualitatively different effect of the preliminary induction of OMF with phenobarbital on the acute toxicity of the noxae studied: lack of effect for DGA, increase for sodium nitrite and decrease for their combination.

Topics: Animals; Biotransformation; Enzyme Induction; Guanidines; Lethal Dose 50; Liver; Male; Mixed Function Oxygenases; Nitrites; Nitroso Compounds; Oxidoreductases; Phenobarbital; Rats; Rats, Inbred Strains; Sodium Nitrite

Adult Swiss mice were treated intragastrically during the last week of pregnancy with the fungicide dodecylquanidine acetate (dodine, DGA) together with 0.05% sodium nitrite. The incidence of malignant lymphomas, lung adenomas and hepatomas was 30--70% in females. The first tumors appeared 4 months after delivery in the FO generation and at 6--7 months in the F1 generation. Among the untreated control mice the frequency of spontaneous tumors was 6%, and lymphomas developed, if at all, only after 10 months. The oncogenic activity of DGA with sodium nitrite in the offspring was dependent on the dose of DGA.A and C type RNA virus particles were demonstrated in lymphomas by electronmicroscopy. DGA alone had no effect on the cancer incidence.

Topics: Animals; Carcinogens; Drug Synergism; Female; Fungicides, Industrial; Guanidines; Inclusion Bodies, Viral; Lymphoma, Non-Hodgkin; Male; Maternal-Fetal Exchange; Mice; Nitrites; Pregnancy; Sarcoma, Experimental; Sex Factors; Sodium Nitrite