Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity.

7-Methylguanine (7-MG) competitively inhibits the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and RNA-modifying enzyme tRNA-guanine transglycosylase (TGT) and represents a potential anticancer drug candidate. Furthermore, as a natural compound, it could escape the serious side effects characteristic for approved synthetic PARP inhibitors. Here we present a comprehensive study of toxicological and carcinogenic properties of 7-MG.

[Investigation of the content of carcinogenic compounds in commercial smoked fish].

The authors performed investigations of the content of polycyclic aromatic hydrocarbons (PAH) (n = 17) and their nitro derivatives (n = 5) in commercial cold and hot smoked herrings and greenlings. The level of benz(a)pyrene in all fish samples was found to be well below the current sanitary and hygienic limits. The concentration of N-nitrosoamines in cold smoked fish was slightly below that in hot smoked one.

[Studies of mutagenic activity of positively charged alkyl glycerolipids in Ames test].

Mutagenic activity of non-phosphorous cationic alkyl glycerolipid rac-N-{4-[(2-Methoxy-3-octadecyloxy)propyl]oxycarbonylbutyl}-N,N-dimethyl-N-(2-hydroxyethyl) ammonium iodide was evaluated. According performed Ames assay results indicated on non-mutagenic properties tested compound. Resulting data open the possibility to carry out biological study in vivo for class of ether cationic glycerolipids and further applications as a potential agent of anticancer therapy.

[Evaluation of the carcinogenic activity of phenol-free coal-tar creolin].

When orally administered to rats and mice, phenol-free coal-tar creolin containing 0.018+/-0.002 g/kg of benz(a)pyrene showed no carcinogenic activity.

[Carcinogenic components of smokeless tobacco and tobacco-free cigarettes].

The investigation deals with an assessment of carcinogenicity and mutagenicity of samples of smokeless tobacco now on the Russian market as well as ash from alternative cigarettes made of aromatic herbs. Our data showed that the levels of polycyclic aromatic hydrocarbons, volatile and tobacco-specific N-nitrosoamines complied with the standards in the producer-countries. Smokeless tobacco extracts failed to show (Ames) any mutagenic effects such as the "read-out frame shift" or "base-pair replacement" patterns.

[Content of N-nitrosamines in smoked fish and canned food].

The composition and contents of major N-nitrosoamines (NA) in the edible part of herrings and rock trouts exposed to hot and cold smoking and in the Smoked fish in oil type cans were studied. Among NA, only N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) were detected in all samples. In the cold-smoked fish, the levels of NDMA and NDEA were higher than in the hot smoked fish and cans.

[Study of carcinogenic hazards of smoking kiln waste fumes].

The disperse phase of waste fumes forming during cold and hot fish smoking was studied by distributing the particles into 6 fractions and determining benz(a)pyrene (BP) in them. The level of BP in less than 2.5 mu was shown to be 85% whether smoking was hot or cold.

[Characterization of the content of polycyclic aromatic hydrocarbons in the cold- and hot-smoked fish].

The carcinogenic danger of the commercial smoked herring was assessed. The edible part of the smoked herring contains 16 polycyclic aromatic hydrocarbons whose bulk consists of phenanthrene, pyrene, floranthene, and benzo(b)fluoranthene. The content of benzo(a)pyrene (BP) in the cold and hot smoked herring are 189 and 291 ng/kg, respectively.

Genotoxicity and carcinogenicity testing of 1,2-dibromopropane and 1,1,3-tribromopropane in comparison to 1,2-dibromo-3-chloropropane.

The activities of 1,2-dibromopropane (DBP) and 1,1,3-tribromopropane (TBP) were studied in seven genotoxicity assays, (i) SOS-induction in E. coli, (ii) DNA repair in primary rat hepatocyte culture, (iii) the Salmonella/microsome assay, (iv) a host-mediated assay using Salmonella, (v) the somatic mutation and recombination assay in Drosophila melanogaster, (vi) HGPRT-mutagenesis assay in ARL 18 cells, and (vii) micronucleus formation assay in mouse polychromatophylic erythrocytes (PCE), forestomach (FS), glandular stomach (GS), duodenum (D), jejunum (J), cecum (C) and liver (L). The halopropanes were also tested for tumor formation in the fish Danio rerio.

The clastogenic and mutagenic effects of ascorbigen and 1'-methylascorbigen.

Ascorbigen, which occurs naturally in the human diet, and a synthetic analogue (1'-methylascorbigen), were assayed for cytotoxic and clastogenic activities in a SV40-transformed Indian Muntjac cell line (SVM), and for mutagenic activity in the Ames test using Salmonella typhimurium strains TA98 and TA100. Ascorbigen had no effect upon the clonal survival of SVM at concentrations below 0.21 mg/ml and did not induce either chromosome aberrations or sister-chromatid exchanges (SCEs) at any concentration tested up to the maximum compatible with the assay conditions; nor did it induce mutations in either Salmonella strain.

A Drosophila simulans mutant strain sensitive to benzo[a]pyrene and 2-acetylaminofluorene.

We have identified a Drosophila simulans mutant, 364 yu, that is sensitive to the toxic effects of the procarcinogens B(a)P and 2-AAF. Heterozygotes obtained by crossing it to the wild resistant Turku strain (female 364 yu x male Turku) were more sensitive than heterozygotes obtained from the reciprocal cross (female Turku x male 364 yu) to both the toxic and the mutagenic effects of B(a)P in Drosophila tests that measured lethality and the induction of somatic mosaicism, respectively. The non-carcinogens pyrene, B(e)P and 4-AAF were only weakly toxic and non-mutagenic.

[The mutagenic activity of coal tar].

Genotoxicity of tar samples collected at the Kemerovo and Altai by-product coke plants has been studied, the contribution of benz(a)pyrene (BP) into the total mutagenic activity of extracts being estimated. Both direct and indirect mutagenicity of the samples is determined in the Ames test. A direct mutagenic effect of coal tar may be attributed neither to the BP action nor to other polycyclic aromatic hydrocarbons.

[Direct-action mutagens in exhausts of vehicles with diesel engines].

The genotoxic activity of exhausts from one-shaft gas-turbine GTE-5 engine (30 kW) and a standard D-54A diesel (40 kW) have been studied. Thus, the extracts of soot from GTE-5 and D-54A induced reversions in Salmonella typhimurium both with and without metabolic activation: furthermore, extracts of soot from GTE-5 demonstrated a higher mutagenic activity. The direct mutagenic effect of the exhausts depended neither on the presence of BP nor on the other polycyclic aromatic hydrocarbons (PAHs).

[Distribution, formation, carcinogenic and mutagenic activities of nitro derivatives of polycyclic aromatic hydrocarbons].

Nitro-PAHs (nitro-substituted derivatives of polycyclic aromatic hydrocarbons) are a class of chemical compounds with high biologic activity. They have been detected in samples of air pollutants, diesel and gasoline engine exhausts, in airplane exhaust emissions, cigarette smoke condensate, emissions of coke ovens, wood-burning fireplaces, coal-fired plants, in food and tea. Concentrations of nitro-PAHs have been compared with those of PAHs present in air pollutant samples and emissions from different sources.

[Polycyclic aromatic hydrocarbon content of waste products of the coal-tar industry and the mutagenic effect of soot extracts].

The content of 15 polycyclic aromatic hydrocarbons (PAH) in organized and nonorganized effluents of cake- and by-product processes at the Rustavi integrated iron-and-steel works was quantitatively determined by the method of low-temperature spectrofluorescence. Contents of BP and other PAH in nonorganized effluents is 100 and more times higher than those in the organized one and play a decisive role in pollution of the low atmospheric layer. The effluent is characterized by a specific PAH composition and therefore BP may be both a quantitative and a qualitative indicator of PAH.

[Mechanisms of the toxic effect of benz(a)pyrene and its derivatives in tissue culture].

Study in cell cultures of toxic action and metabolism of benz(a)pyrene and its derivatives substituted in the 6th position has shown that the toxic effect of the compounds depends on the substituent moiety. No correlation has been disclosed between toxicity and metabolism intensity. It is suggested that toxic action of benz(a)pyrene and its 6-substituted is determined by epoxide formation in the 4th-5th position.

[Mutagenic action of benz(a)pyrene and its metabolites in the in vitro Salmonella typhimurium-microsomes test system].

It has been shown that epoxides are responsible for the mutagenic action of benz(a)pyrene in the system. S. typhimurium.