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A Rannug

Publications and source records attributed to A Rannug.

43 records · Page 3Linked to original sources
PubMed1987

Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances.

The purpose of the present study was to determine whether ultraviolet light (UV) irradiation of amino acids produces compounds with affinity for the Ah receptor. Aqueous solutions of L-tryptophan were exposed to radiation from an unfiltered high-pressure mercury lamp. The photoproducts formed were solvent-extracted or concentrated on Sep-Pak C18 cartridges. The concentrated extracts or eluants were treated for their ability to compete with 3H-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Binding was assayed in liver cytosolic preparations from Sprague-Dawley rats using a technique based on hydroxylapatite separation. Photoproducts with receptor affinity were formed in a time-dependent manner. Histidine and tryptamine also gave products upon UV irradiation that competed with TCDD. Commercial tryptophan, at least aged, contained trace amounts of impurities with receptor affinity. Analysis by TLC and high-pressure liquid chromatography of the photo-products of tryptophan showed a minimum of three different binding compounds. Two of the products were studied in greater detail. One of them, showing UV absorbance and yellow fluorescence, gave a molecular ion (M+) of 284 and the other gave M+ 312 but showed little UV absorption and fluorescence. The concentration, based on mass spectrometry quantifications, of the two compounds that displaced more than 50% of TCDD was found to be extremely low, giving Kd values of 0.44 nM (M+ 312) and 0.07 nM (M+ 284). The existence of high affinity receptors for oxidized amino acids is postulated and their possible role in the proliferative cellular responses to TCDD and tryptophan is discussed briefly.

Amino Acids↗
PubMed1984

Enzyme inhibition as a possible mechanism of the mutagenicity of dithiocarbamic acid derivatives in Salmonella typhimurium.

In recent years data have accumulated regarding genotoxic properties of dithiocarbamic acid derivatives. The results from the present work indicate that the mutagenicity of these compounds depends on an indirect effect via oxygen radicals. Mutagenicity of tetramethylthiuram disulfide ( TMTD ), that was used as a model substance, was established with both frameshift and base substitution sensitive strains of Salmonella typhimurium. Addition of copper ions resulted in a decreased survival at low dithiocarbamate doses. The dose response curves seem to correlate with the formation of two types of metal dithiocarbamate complexes. At low doses charged complexes are formed, while the formation of uncharged complexes is favoured at higher dosages. The data suggest that this formation of uncharged metal complexes implies a decreased toxicity but at the same time an increased mutagenicity. The mutagenicity of both TMTD and its ethyl analogue TETD was enhanced by oxygen. Furthermore, TMTD potentiates the mutagenic action of menadione, a substance that produces O(2) and H2O2 by redox cycling with molecular oxygen. Interaction of uncharged metal dithiocarbamate complexes with both production and detoxification of reactive forms of oxygen is suggested to be responsible for the direct mutagenic effects via oxidative damage to DNA. A further enhancement of the oxygen radical content of the cells by adding microsomes that produce oxygen radicals via autoxidation of cytochrome P-450 is proposed as the mechanism for the 'metabolic activation of TMTD '.

Animals↗
PubMed1984

Some chloro derivatives of polynuclear aromatic hydrocarbons are potent mutagens in Salmonella typhimurium.

A series of chlorinations of some polynuclear aromatic hydrocarbons (PAH) were carried out and the products were tested for mutagenicity on Salmonella typhimurium TA98 and TA100. We conclude that the chlorination of certain PAHs with low mutagenicity, such as pyrene and benzo[e]pyrene, resulted in the formation of two types of product. The chlorination of pyrene was studied in some detail. The major products of this chlorination were chloro-substituted pyrenes. These compounds showed an S9-dependent mutagenicity and were identified as 1-chloro-, 1,6-dichloro-, 1,8-dichloro- and 1,3-dichloropyrene. On tester strain TA100 the mutagenic effect ranged from 1.4 to 14 revertants/nmol, 1,3-dichloropyrene being the most potent of the isomers. Minor products eluting from a chromatograph in a more polar fraction than the major products were also formed. These compounds were less stable than the major products and were identified as pyrene with chloro additions in the 4- and 5-positions, with various chloro substituents at other positions. These minor products showed a high mutagenic effect on Salmonella in the absence of S9. The mutagenic effect on strain TA100 ranged from 10 to 15 revertants per ng which is at least 40 and 4000 times higher than for 1-nitropyrene and pyrenequinones, respectively. These unstable chloro derivatives of pyrene are difficult to analyse chemically because they are easily degraded and give rise to the more stable 4-chloropyrene.

Mass Spectrometry↗
PubMed1983

Mutagenicity of rubber additives and curing fumes. Results from five short-term bioassays.

The mutagenicity of rubber additives and curing fumes from some rubber formulations were studied in five short-term tests: point mutations in Chinese hamster V79 cells, the induction of sister chromatid exchanges in Chinese hamster ovary cells, micronuclei in erythrocytes of Chinese hamster bone marrow, sex-linked recessive lethal mutations in Drosophila melanogaster, and reverse mutations in the Salmonella/microsome assay. When 46 rubber additives were tested with Salmonella, 15 compounds were mutagenic, 16 were negative, and 15 were negative with no observed toxicity. Only one negative response was obtained for the nine tested samples of curing fumes. Thiuram and dithiocarbamate additives and some curing fumes with mutagenic responses in Salmonella were the primary objects of study in the other four test systems. Although the results of these four tests did not completely parallel the Salmonella results, they indicate that the individual compounds and the curing fumes from different types of rubber formulations may involve genotoxic risks.

Air Pollutants, Occupational↗
PubMedDate not supplied

Protection from toxic and mutagenic effects of H2O2 by catalase induction in Salmonella typhimurium.

Demple and Halbrook (1983) have reported that pretreatment of E. coli with H2O2 induces protection against the toxic effects of subsequent treatment with H2O2, which cannot be attributable to catalase induction, but rather to inducible repair of oxidative DNA damage. Here we report that pretreatment of Salmonella typhimurium with small doses of H2O2 also renders them resistant to subsequent higher doses of H2O2. However, this induced protection against H2O2, both concerning survival and mutations, is proportional to the amount of induced catalase activity of the bacteria, which accelerates the breakdown of H2O2 in the medium, thus lowering the effective dose.

Catalase↗
PubMedDate not supplied

Association between the p21 codon 31 A1 (arg) allele and lung cancer.

In previous investigations p53 polymorphisms and haplotypes have been found to be associated with different types of cancer. In this paper the codon 31 polymorphism of the p53-inducible protein p21 was studied in 144 Swedish lung cancer patients and two different control groups: 95 patients with chronic obstructive pulmonary disease (COPD) and 761 healthy controls. An increased frequency of the p21 codon 31 A1 (arg) allele was found in lung cancer patients, especially in comparison with COPD patients (p = 0.004). There was a significantly increased frequency among lung cancer patients of individuals carrying the arg allele both in comparison with COPD controls (OR = 5.2, 95% CI 1.5-18.1) and healthy controls (OR = 1.7, 95% CI = 1.0-2.9). The results of this and previous studies indicate that allelic variants of both p53 and its effector protein p21 may have an influence on lung cancer.

Alleles↗