The effect of fractionated exposure to unequal concentrations of chemical mutagens

The effect of unequally fractionated concentrations of dipin and thiophosphamid on chromosomes of human lymphocytes was investigated at Go phase. There were used five low concentrations of mutagens 2, 0.2, 2.10(-2), 2.10(-3), 2.10(-4) mcg/ml and one high concentration 20 mcg/ml by which cells have been treated. Decrease of chromosome breaks and exchanges were observed, but the level of the aberration cell was stable. The "protective" levels for dipin were in concentrations of 0.2, 2.10(-2), 2.10(-3) mcg/ml. Only one "protective" concentration was 2.10(-2) mcg/ml.     

Effects of paving asphalt fume exposure on genotoxic and mutagenic activities in the rat lung

Asphalt fumes are complex mixtures of aerosols and vapors containing various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). Previously, we have demonstrated that inhalation exposure of rats to asphalt fumes resulted in dose-dependent induction of CYP1A1 with concomitant down-regulation of CYP2B1 and increased phase II enzyme quinone reductase activity in the rat lung. In the present study, the potential genotoxic effects of asphalt fume exposure due to altered lung microsomal enzymes were studied. Rats were exposed to air or asphalt fume generated under road paving conditions at various concentrations and sacrificed the next day. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and examined for DNA damage using the comet assay. To evaluate the systemic genotoxic effect of asphalt fume, micronuclei formation in bone marrow polychromatic erythrocytes (PCEs) was monitored. Lung S9 from various exposure groups was isolated from tissue homogenates and characterized for metabolic activity in activating 2-aminoanthracene (2-AA) and benzo[a]pyrene (BaP) mutagenicity using the Ames test with Salmonella typhimurium YG1024 and YG1029. This study showed that the paving asphalt fumes significantly induced DNA damage in AM, as revealed by DNA migration in the comet assay, in a dose-dependent manner, whereas the micronuclei formation in bone marrow PCEs was not detected even at a very high exposure level (1733 mg h/m3). The conversion of 2-AA to mutagens in the Ames test required lung S9-mediated metabolic activation in a dose-dependent manner. In comparison to the controls, lung S9 from rats exposed to asphalt fume at a total exposure level of 479+/-33 mg h/m3 did not significantly enhance 2-AA mutagenicity with either S. typhimurium YG1024 or YG1029. At a higher total asphalt fume exposure level (1150+/-63 mg h/m3), S9 significantly increased the mutagenicity of 2-AA as compared to the control. However, S9 from asphalt fume-exposed rats did not significantly activate the mutagenicity of BaP in the Ames test. These results show that asphalt fume exposure, which significantly altered both phases I and II metabolic enzymes in lung microsomes, is genotoxic to AM and enhances the metabolic activation of certain mutagens through altered S9 content.     

The effect of different genetic properties of Salmonella typhimurium on the determination of stabilities and mutagenic concentrations of chemical carcinogens using the diffusion bioassay

The mutagenic sensitivity of SV50, the R-factor plasmid containing tester, of the Salmonella/arabinose-resistant assay system has been evaluated with different environmental complex mixtures, including extracts of airborne and diesel emission particles, oil-shale ash, nitrosated coal dust and water samples. The mutagenicities of all extracts were detectable with this assay. This study indicates that the arabinose-resistant assay with SV50 is useful for the detection of the mutagenic activity of environmental complex mixtures.     

Calculation of molecular integrals over Slater-type orbitals using recurrence relations for overlap integrals and basic one-center Coulomb integrals

The recurrence relations are established for the basic one-center Coulomb integrals over Slater-type orbitals (STOs). These formulae and the recurrence relations for basic overlap integrals are utilized for the calculation of multicenter electron-repulsion integrals. The calculations of multicenter electron-repulsion integrals are performed by the use of translation formulae for STOs obtained from the Lambda and Coulomb Sturmian exponential-type functions (ETFs). It is shown that these integrals show a faster convergence rate in the case of Coulomb Sturmian ETFs. The accuracy of the results is quite high for the quantum numbers of STOs and for the arbitrary values of internuclear distances and screening constants of atomic orbitals.     

Further evidence for a high position-specific effect in the action of chemical mutagens on the chromosomes of barley

Summary B1 and B2 are small, circular, mitochondrial plasmid-like DNAs found in male-sterile cytoplasm (cms-Bo) of rice. In this study, nuclear sequences homologous to these DNAs were investigated among a number of rice cultivars. Several copies of nuclear B1-and B2-homologous sequences were detected in all examined cultivars, regardless of the presence or absence of the B1 and B2 DNAs in mitochondria, indicating that the existence of the B1- and B2-homologous sequences in the rice nuclear genome was widespread. A restriction fragment length polymorphism (RFLP) was detected for both sequences, and we propose that these DNAs could be useful RFLP markers for the rice nuclear genome. To analyze these nuclear homologues genetically, segregation analysis of the RFLP was carried out in the F₂ progenies of an Indica-Japonica rice hybrid. Of the B1 homologues, there were two nonallelic fragments, one specific to the Indica parent and the other to the Japonica. These results indicate that the B1 and B2 homologues were dispersed in the nuclear genome. The integration of B1-homologous DNA into the nuclear DNA may have occurred independently after sexual isolation of the Indica and Japonica rice varietal groups, or a intranuclear transposition of these sequences took place during the process of rice differentiation into the varietal groups.     

The mutagenic action of nitroimidazoles: IV. A comparison of the mutagenic action of several nitroimidazoles and some imidazoles

The mutagenic action of 51 imidazoles was investigated. The fluctuation test of Luria and Delbrüick was used, with Klebsiella pneurnoniae as test organism. 8 compounds, including 5 with a weak mutagenic action in the fluctuation test, were also investigated by the Ames test in which Salmonella typhimurium TA100 was used.Of the 51 imidazoles examined, 33 were nitroimidazoles. 31 of the latter appeared to be mutagenic, whereas out of the 18 other imidazoles without a nitro group only 2 were mutagenic. Several of the substances tested for mutagenicity showed an antimicrobial activity. No direct relationship between antimicrobial action, growth inhibition and mutagenicity was established.With methyl-nitroimidazoles a relationship was found between the chemical structure and mutagenic action. However, when the nitroirnidazoles had a more complex chemical structure, a relationship between this structure and mutagenicity could not be established.     

The mutagenic action of nitroimidazoles. IV. A comparison of the mutagenic action of several nitroimidazoles and some imidazoles.

The mutagenic action of 51 imidazoles was investigated. The fluctuation test of Luria and Delbrück was used, with Klebsiella pneumoniae as test organism. 8 compounds, including 5 with a weak mutagenic action in the fluctuation test, were also investigated by the Ames test in which Salmonella typhimurium TA100 was used. Of the 51 imidazoles examined, 33 were nitroimidazoles. 31 of the latter appeared to be mutagenic, whereas out of the 18 other imidazoles without a nitro group only 2 were mutagenic. Several of the substances tested for mutagenicity showed an antimicrobial activity. No direct relationship between antimicrobial action, growth inhibition and mutagenicity was established. With methyl-nitroimidazoles a relationship was found between the chemical structure and mutagenic action. However, when the nitroimidazoles had a more complex chemical structure, a relationship between this structure and mutagenicity could not be established.     

Relation between the cytogenetic effect and the dose of radiation and chemical mutagenic exposure of somatic cells in vivo: effect of the duration of exposure and cell selection

Dose-response relationships obtained in vivo in mammalian cells or in vitro when studying structural chromosome aberrations in somatic cells may be used for monitoring human populations exposed to mutagenic agents. While the method appears of interest for biological dosimetry on people exposed to relatively high doses of ionizing radiation, its value for persons professionally exposed to chemicals is, however, limited.     

Studies on the mutagenic action of formaldehyde in Drosophila

Summary Drosophila males were exposed to a sublethal concentration of cyanide gas prior to the injection of formaldehyde solutions. Compared to the controls which only received formaldehyde the frequency of sex-linked lethals was increased after the cyanide pretreatment in altogether six independent experiments. These results are taken as further proof that formaldehyde exerts at least part of its mutagenic effects via the formation of peroxides. It is suggested that an excessive amount of hydrogen peroxide, due to inhibition of the cytochrome and catalase enzyme systems, favours the formation of a mutagenic, organic peroxide, presumably dihydroxydimethyl peroxide. The fact that formaldehyde exerts an inhibiting effect on catalase in its own right might be of importance for the interpretation of its mutagenic action.It was also observed that after cyanide pretreatment, the mutagenic effectiveness of a mixture of formaldehyde and hydrogen peroxide was lower than that of formaldehyde alone. These findings can be interpreted by assuming that high concentrations of dihydroxydimethyl peroxide or of a combination of cyanide and this peroxide, eliminate selectively germ cells with induced mutations. It is possible that the same explanation applies to the low mutagenic effectiveness of a mixture of formaldehyde and hydrogen peroxide compared with that of formaldehyde alone when both are preceded by cyanide.With 3 figures in the text     

Different effect of hyperthermia and heat shock on the action of quinolone drugs versus some mutagens against chloroplasts of Euglena gracilis

Hyperthermia (37 degrees C permanently) and heat shock (42 degrees C for 10 min, and then 27 degrees C) retarded the elimination of chloroplasts from the flagellate Euglena gracilis induced by quinolone antibacterial chemotherapeutics (OA, NA, Cnx, Ofx, Cpfx, Enx, Nfx) in comparison with their action at 27 degrees C. In the case of OA, NA, and Cnx those hyperthermic conditions completely blocked their action against chloroplasts. On the other hand, both temperature regimes accelerated the antichloroplast activity of the mutagens/carcinogens nitrosoguanidine and furylfuramide.