Biomedical subjects
Publications and source records attributed to A D Durnev.
The chromosome aberration assay in the bone marrow cells of C57BL/6 mice showed that melanin pigment (MP) in a dose range from 0.01 to 10 mg/kg does not influence the clastogenic effect of dioxidine (200 mg/kg, i.p.), while reducing the clastogenic effect of cyclophosphamide (20 mg/kg, i.p.) by a factor of 1.5-4 in various treatment regimes depending on the mutagen injection time.
The method of fluorometric analysis for DNA unity (FADU) was used to study the genotoxic effects of cyclophosphamide in rats. The dose dependence and time variation of mutagenicity manifestations in various organs and tissues of the experimental animals was studied. It was established that FADU results agree with the data obtained by conventional methods of cytogenetics. The results confirm the expediency of using FADU for the preclinical investigations of drugs.
Himantane introduced via a gastric tube to pregnant rats in a dose of 10, 30, 50, and 100 mg/kg produced a dose-dependent embryotoxic and teratogenic action. An analysis of the experimental results and published data suggests that the embryotoxicity of himantane can be related to its general toxic action upon the organism of pregnant female rats.
Effect of the new potential antiparkinsonian drug hemantane (N-(adamant-2-yl)hexamethyleneimine hydrochloride) on the generative function and gonad morphology was studied in a group of male and female mongrel rats. The generative function was studied after peroral drug administration in a dose of 10 mg/kg (ED50) and 50 mg/kg (5 ED50): males were treated over a 60-day period of spermatogenesis, while females received the drug in the same doses over 15 days (three estrous cycles). The gonad morphology was studied after a 6-month treatment of experimental animals with hemantane in the same doses. It was established that the administration hemantane in indicated doses did not influence the generative function and gonad morphology in male and female rats.
Melanins are polyphenolic pigments of plants, animals and microbes with antioxidant and antiradiation activity. Water-soluble melanin from buckwheat is experienced as antimutagenic means (0.01-10 mg/kg per os) for cyclophosphamide (20 mg/kg i.p.) in the 3 series of experiments. The frequency of chromosome aberrations in the cells of mice bone marrow after mutagene is reduced 2-6 times once under influence of melanin.
Non-narcotic analgetics sodium diclofenac, indomethacin, naproxen, nimesulid, ketorolac, and celebrex (cytochrome P-450(2)c substrates) produce more pronounced and prolonged analgesic effect in pubertate female rats than in males. This can be related to the slower elimination of drugs from the female organism. The liver of females is characterized by a lower content of cytochrome P-450 and by less pronounced activity of amidopyrine-N-, indomethacin-O-, and naproxen-O-demethylase activity. No sex-related differences in pharmacodynamics were observed for meloxicam, and ethoricoxib, benzofurocaine, and amison, and acetylsalicylic acid, which are the substrates predominantly for CYP3A.
The chromosome aberration assay in the bone marrow cells of C57BL/6 mice was used to study the cytogenetic activity of ribavirin (10, 50, 100, 200, and 400 mg/kg, p.o.) alone and in combinations with verapamil (0.25, 2.5, 5, and 10 mg/kg, p.o.). It was established that ribavirin was cytogenetically active upon single administration in a dose of 200 and 400 mg/kg, and it was also active in a dose of 50 and 100 mg/kg when administered for 5 days in combination with verapamil in a dose of 5 or 10 mg/kg and 2.5, 5, or 10 mg/kg, respectively. These results indicate that verapamil and ribavirin exhibit comutagen action.
The study of the genotoxic activity of ethidium bromide and bleomycin by the two methods in Drosophila melanogaster showed that both drugs possess the mutagenic activity. The comparison of the data obtained for both drugs by the methods of recessive, sex-linked, lethal mutations and somatic mosaicism indicates the quantitative and qualitative similarity of their mutagenic action. The results make it possible to regard the method of somatic mosaicism as a promising test for primary evaluation of mutagenic properties of chemical compounds.
The effects of ubiquinone-10 given in oral doses of 0.2-20 mg/kg on cytogenetic effects of intraperitoneal photrinum (7 and 14 mg/kg), dioxydinum (100 and 300 mg/kg) and cyclophosphanum (20 mg/kg) were studied in the bone marrow metaphasic cells of male C57Bl/6 mice. Ubiquinone-10 (2 to 20 mg/kg) statistically significantly reduced the clastogenic action of these mutagens, except photrinum used in a dose of 7 mg/kg. The antimutagenic effect of the drug was dose-independent and no more than 50%. The findings enable ubiquinone-10 be considered as an endogenous antimutagen. It is suggested that the antimutagenic activity of the compound is due to its antioxidative properties.
Ability of adenosine, caffeine, theophylline, cAMP, dimephosphone, PABA and tocopherol acetate to modify the rate of mutagenesis induced as well as to affect the content of endogenous cAMP were studied in experiments with seeds of Crepis capillaries. Those concentrations of these drugs which decreased the rate of mutations, were shown to increase the content of endogenous cAMP in the seeds. Higher concentrations of the drugs did not exhibit any antimutagenic activity as well as did not contribute to an increase in the cAMP content, but sometimes decreased distinctly cyclonucleotide content in the seeds.
The cytogenetic activity of food dyes was examined in the experiments on male C57B1/6 mice which were orally given during 5 days the following daily doses: Tartrasine (E102), 0.5 and 5.0 mg/kg; Indigo carmine (E132), 1.4 and 14 mg/kg; Canset yellow (E110), 0.17 and 1.7 mg/kg; Cochenillerot A (E124), 0.63 and 6.3mg/kg; Azorubin (E122), 1 and 10 mg/kg and Patentblau V (E131), 0.08 and 0.8 mg/kg. Five hundred metaphase slides each were analyzed in the control and experimental test series. The findings may conclude that the dyes tested within the above dose ranges do not induce any increase in the level of cells with chromosomal damages in the inbred animals.
Phorbol-myristate acetate- and opsonized zymosan-induced statistically significant differences were shown in the intensity of chemiluminescence occurring in the bone marrow cell suspension. The bone marrow cells from male BALB/c mice showed the most pronounced response to stimulation in the two cases. After 5-day administration of dioxidine (300 mg/kg), the number of the injured metaphases in the bone marrow from the examined animals was 43.6 +/- 2.2 and 23.8 +/- 1.9% in BALB/c and C57B1/6 mice, respectively, which provides evidence for marked strain-specific differences in the cytogenetic effect of this proxidative mutagen. The findings indicated that there was a relationship between the capacity of bone marrow cells of producing APA and the severity of cytogenetic lesions in these cells.
The present paper describes the possible clastogenic activity of the following synthetic sugar substitutes, such as cyclamate in daily doses of 11 and 110 mg/kg, saccharin, 5 and 50 mg/kg, acesulfam, 15 and 150 mg/kg, sucralose, 15 and 150 mg/kg, aspartame, 40 and 400 mg/kg, orally given to C57Bl/6 mice during 5 days. No clastogenic activity was found in the compounds tested.
The method of chromosome aberration scoring in the bone marrow cells of C57BL/6 mice was used to study the influence of apo-carotene (AC) on the clastogenic effect of intraperitoneal injections of the following two mutagens: cyclophosphamide (CP) in a dose of 30 mg/kg and dioxidine (DN) in a dose of 300 mg/kg. AC was given per os as a food dye E160L (20% oil suspension) in doses of 0.5, 5, and 50 mg/kg (0.1, 1.0 and 10 mg/kg, respectively, on conversion to pure apo-carotene). The experiment was conducted in three variants: in simultaneous injection of the compounds for 24 h, injection of the mutagens for 24 h in 5-day treatment of the animals with AC, and in combined 5-day administration of AC and mutagens and killing of the animals 6 h after the last administration. In all variants a 10 mg/kg dose of AC reduced the clastogenic effect of CP and DN. Moreover, the clastogenic effect of CP was reduced in pretreatment of the animals with AC in a dose of 1 mg/kg, and that of DN when it was combined with AC in a dose of 0.1 mg/kg for 5 days and in pretreatment of the animals with AC in a dose of 1.0 mg/kg.
The article deals with the results characterizing the state of Russian and foreign elaborations in the study of genotoxic effects of drugs and immunobiological agents. Particular attention is placed on general problems of strategy and tactics in the study of mutagenicity of drugs the solution of which is insufficiently substantiated or insufficiently discussed in the literature. The perspective problems of research into the field of genotoxicity of drugs are discussed.
Cytogenetic study conducted after a single intraperitoneal injection of cyclophosphane in doses of 10, 20, and 40 mg/kg showed in 1.5-2-month-old male mice that the level of bone marrow cells damaged by the mutagen was significantly higher in NZW animals than in C57Bl/6 animals. The ability to produce active oxygen forms in response to addition of opsonized zymosan and phorbol myristate acetate was also higher in bone marrow suspensions of NZW mice. The higher sensitivity of NZW animals to pro-oxidant and clastogenic effects may be related to the genetically determined decrease of antioxidant protection in NZW animals.