PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “SOS Response, Genetics”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed2002

Genotoxicity of 5-aminolevulinic and 4,5-dioxovaleric acids in the salmonella/microsuspension mutagenicity assay and SOS chromotest.

5-Aminolevulinic acid (ALA) is a heme precursor that accumulates in some porphyric disorders and in lead poisoning which can undergo metal-catalyzed oxidation producing reactive oxygen species and the keto-aldehyde, 4,5-dioxovaleric acid (DOVA). Evidence in vitro of ALA-induced DNA lesions suggests that ALA and DOVA have mutagenic potential that could possibly contribute to an increased frequency of hepatocellular carcinoma (HCC) in patients with acute intermittent porphyria (AIP). In this study, we evaluated the genotoxic potential of ALA and DOVA. In the absence of exogenous metabolic activation, ALA and DOVA were mutagenic in Salmonella typhimurium tester strain TA104. ALA was also mutagenic in S. typhimurium TA102, but not in TA98, TA100, or TA1535, indicating an oxidative mechanism. Removal of H(2)O(2) with catalase gave only partial protection, suggesting generation of other mutagenic species. Both ALA and DOVA damaged the DNA of Escherichia coli PQ37, inducing the SOS response detected by an increase in beta-galactosidase activity. These results verified the potential mutagenic activity of ALA and DOVA and reinforce the hypothesis that DNA damage induced by ALA may be associated with the development of HCC in individuals suffering from AIP.

Aminolevulinic Acid↗
PubMed2002

Induction of the SOS response in starved Escherichia coli.

The SOS system in Escherichia coli is induced in response to DNA damage and the arrest of DNA synthesis. Here we show that in AB1157 bacteria starved for arginine, conditions for induction of adaptive mutations, the LexA-dependent SOS system is induced, but that this occurs only when the bacteria resume growth and when the source of carbon is glycerol rather than glucose (glycerol, but not glucose, enables synthesis of cAMP). Therefore, we conclude that starved cells accumulate some lesions in DNA, which in growth conditions may trigger SOS induction by a process that is cAMP-dependent.

Actin Cytoskeleton↗
PubMed2003

E. coli BW535, a triple mutant for the DNA repair genes xth, nth, and nfo, chronically induces the SOS response.

A strong chronic induction of the SOS response system occurs in E. coli BW535, a strain defective in nth, nfo and xth genes, and hence severely deficient in the repair of abasic sites in DNA. This was shown here by visualization of filamentous growth of the BW535 strain and by measuring the level of beta-galactosidase expressed in BW535/pSK1002 in comparison to the AB1157/pSK1002 strain. The plasmid pSK1002 bears an umuC::lacZ fusion in which lacZ is under the control of the umuC promoter and regulated under the SOS regulon. Increases in the expression of beta-galactosidase occur in BW535 without any exogenous SOS inducer. Chronic induction of the SOS response was observed previously in E. coli strains bearing mutations in certain genes that have mutator activity and BW535 is a moderate mutator strain. However, not all mutators show this property, since chronic induction of SOS was not observed in mutT or mutY mutators. MutT and MutY proteins, when active, protect bacteria from mutations induced by 8-oxoG lesions in DNA. This suggests that accumulation of abasic sites, but not 8-oxoG residues in DNA, induce the SOS response.

Carbon-Oxygen Lyases↗
PubMed2003

Evaluation of mutagenic activity in an extract of pepper tree stem bark (Schinus terebinthifolius Raddi).

An extract (decoction) from pepper tree stem bark (Schinus terebinthifolius Raddi) is widely used in Brazil as a topical antiinflammatory agent and to cicatrize wounds. The extract contains catechin, tannins, terpenes, flavonoids, and saponins; of these components, both mutagenic potential and antioxidant properties have been ascribed to flavonoids. The mutagenicity of some flavonoids is believed to be associated with the formation of reactive oxygen species and seems to depend on the number and position of hydroxyl groups. In the present study, we evaluated an extract of S. terebinthifolius in a series of cell-free and bacterial assays in order to determine its genotoxic potential. The extract was negative in a cell-free plasmid DNA test, indicating that it did not directly break DNA. Positive results, however, were obtained in the SOS chromotest, in a forward mutagenesis assay employing CC104 and CC104mutMmutY strains of Escherichia coli, and in the Salmonella reversion assay, using strains TA97, TA98, TA100, and TA102. All the bacterial tests were performed without exogenous metabolic activation due to the topical use of this preparation. The results indicate that pepper tree stem bark extract produces DNA damage and mutation in bacteria, and that oxidative damage may be responsible for the genotoxicity.

Anacardiaceae↗
PubMed2004

Evaluation of the Salmonella umu test with 83 NTP chemicals.

There is a need for simple rapid tests for evaluating the carcinogenic potential of the thousands of chemical compounds that are developed each year. The DNA-damaging effects of 83 National Toxicology Program (NTP) chemicals, including noncarcinogens and carcinogens, were examined in the umu test by measuring the expression of the umuDC-lacZ genes in Salmonella typhimurium TA1535/pSK1002. Salmonella were exposed to individual NTP chemicals at 37 degrees C for 2 hr both with and without a rat liver S9 mix; the treated cells were then diluted and incubated for a further 2 hr (posttreatment assay). O-nitrophenyl-beta-D-galactoside was added to the cultures and the beta-galactosidase activity driven by the Salmonella umuDC-lacZ genes was determined by measurement of the OD(420 nm) and OD(550 nm) of the cultures. Salmonella cell number was simultaneously determined by measurement of OD(600 nm). The overall concordance between genotoxicity in the umu test and carcinogenicity was 67%, which was similar to the concordance between Ames' test results and carcinogenicity (63%) using the same 83 NTP chemicals. The results of this study indicate that the umu test with a single Salmonella strain is a simple rapid system, with accuracy comparable to existing, more time-consuming assays.

Animals↗
PubMed2006

A model for targeted substitution mutagenesis during SOS replication of double-stranded DNA containing cis-syn cyclobutane thymine dimers.

A model for ultraviolet mutagenesis is described that is based on the formation of rare tautomeric bases in pyrimidine dimers. It is shown that during SOS synthesis the modified DNA-polymerase inserts canonical bases opposite the dimers; the inserted bases are capable of forming hydrogen bonds with bases in the template DNA. SOS-replication of double-stranded DNA having thymine dimers, with one or both bases in a rare tautomeric conformation, results in targeted transitions, transversions, or one-nucleotide gaps. Structural analysis indicates that one type of dimer containing a single tautomeric base (TT*(1), with the "*" indicating a rare tautomeric base and the subscript referring to the particular conformation) can cause A:T --> G:C transition or homologous A:T --> T:A transversion, while another dimer (TT*(2)) can cause a one-nucleotide gap. The dimers containing T*(4) result in A:T --> C:G transversion, while TT*(5) dimers can cause A:T --> C:G transversion or homologous A:T --> T:A transversion. If both bases in the dimer are in a rare tautomeric form, then tandem mutations or double-nucleotide gaps can be formed. The dimers containing the rare tautomeric forms T*'(1) , T*'(2), T*'(3), T*'(4), and T*'(5) may not result in mutations. The question of whether dimers containing T*'(4) and T*'(5) result in mutations requires further investigation.

DNA↗
PubMed2007

Antigenotoxic activities of crude extracts from Acacia salicina leaves.

For centuries, plants have been used in traditional medicines and there has been recent interest in the chemopreventive properties of compounds derived from plants. In the present study, we investigated the effects of extracts of Acacia salicina leaves on the genotoxicity of benzo[a]pyrene (B(a)P) and nifuroxazide in the SOS Chromotest. Aqueous, total oligomers flavonoids (TOF)-enriched, petroleum ether, chloroform, ethyl acetate, and methanol extracts were prepared from powdered Acacia leaves, and characterized qualitatively for the presence of tannins, flavonoids, and sterols. All the extracts significantly decreased the genotoxicity induced by 1 microg B(a)P (+S9) and 10 microg nifuroxazide (-S9). The TOF-enriched and methanol extracts decreased the SOS response induced by B(a)P to a greater extent, whereas the TOF-enriched and the ethyl acetate extracts exhibited increased activity against the SOS response produced by nifuroxazide. In addition, the aqueous, ethyl acetate, and methanol extracts showed increased activity in scavenging the 1,1-diphenyl- 2-picrylhydrazyl (DPPH) free radical, while 100-300 microg/ml of all the test extracts were active in inhibiting O2-production in a xanthine/xanthine oxidase system. In contrast, only the petroleum ether extract was effective at inhibiting nitroblue tetrazolium reduction by the superoxide radical in a nonenzymatic O2- -generating system. The present study indicates that extracts of A. salicina leaves are a significant source of compounds with antigenotoxic and antioxidant activity (most likely phenolic compounds and sterols), and thus may be useful for chemoprevention.

Acacia↗
PubMed1987

Mutagenic and lethal effects of near-ultraviolet radiation (290-400 nm) on bacteria and phage.

Despite decades of study of the effect of near-ultraviolet radiation (NUV) on bacterial cells, insights into mechanisms of deleterious alterations and subsequent recovery are just now emerging. These insights are based on observations that 1) damage by NUV may be caused by a reactive oxygen molecule, since H2O2 may be a photoproduct of NUV; 2) some, but not all, of the effects of NUV and H2O2 are interchangeable; 3) there is an inducible regulon (oxyR) that responds to oxidative stress and is involved in protection against NUV; 4) a number of NUV-sensitive mutants are defective either in the capacity to detoxify reactive oxygen molecules or to repair DNA damage caused by NUV; and 5) recovery from NUV damage may not directly involve induction of the SOS response. Since several distinctly different photoreceptors and targets are involved, it is unknown whether NUV lethality and mutagenesis result from an accumulation of damages or whether there is a particularly critical photoeffect. To fully understand the mechanisms involved, it is important to identify the chromophore(s) of NUV, the mechanism of toxic oxygen species generation, the role of the oxidative defense regulon (oxyR), the specific lesions in the DNA, and the enzymatic events of subsequent repair.

Bacterial Proteins↗
PubMed1988

Adaptive response of Escherichia coli to alkylation damage.

Treatment of cells with low levels of alkylating agents for extended periods of time causes them to become resistant to the lethal and mutagenic effects of subsequent high-level challenge treatments with alkylating agents. This increased resistance has been called the adaptive response to alkylation damage and results from the induction of an alkylation-specific DNA repair response. The adaptive response is most efficiently induced by methylating agents and is most effective against the lethal and mutagenic effects of methylation damage to DNA. Four genes have been identified as components of this response, ada, alkA, alkB and aidB. The functions of two of these genes are known. AlkA protein functions as a glycosylase that repairs N3-meA, N3-meG, O2-meT, and O2-meC residues in DNA, and Ada protein functions as an alkyltransferase that removes alkyl groups from O6-meG, O4-meT residues as well as methylphosphotriesters. After it interacts with methylated DNA, Ada protein functions as a positive regulatory element that controls the expression of the adaptive response by stimulating the expression of the ada-alkB operon, and the alkA and aidB genes.

Alkylating Agents↗
PubMed1988

Detection of carcinogenic glutamic acid pyrolysis products in Worcestershire sauce by high-performance liquid chromatography.

Commercially available Worcestershire sauce was analyzed for mutagenic and carcinogenic glutamic acid pyrolysis products using high-performance liquid chromatography. These carcinogenic heterocyclic amines were found to be present in all brands of Worcestershire sauce analyzed. The identity of the carcinogens was confirmed by spectrometric analyses and the SOS umu-test. The concentrations of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) in the Worcestershire sauce were 695 +/- 329 pmol/liter (mean +/- SD, n = 5) and 1,839 +/- 1,321 pmol/liter (n = 5), respectively.

Amines↗
PubMed1988

Mutagenesis of bleomycin-damaged lambda phage in SOS-deficient and repair endonuclease-deficient Escherichia coli.

Previous DNA sequence analysis of bleomycin-induced forward mutations in repackaged lambda phage has suggested SOS-dependent replicative bypass of oxidized apyrimidinic sites as a possible mechanism of mutagenesis. In order to evaluate this hypothesis further, frequencies of mutation to a clear-plaque phenotype were compared for bleomycin-damaged phage grown in various repair-deficient strains of Escherichia coli. Survival of bleomycin-damaged phage was virtually identical in all host strains. Studies in SOS-deficient strains indicated specific requirements for functional recA+ and umuC+ alleles in the generation of the majority of bleomycin-induced mutations, as well as a less stringent requirement for induction of the SOS response by ultraviolet irradiation of the host cells. These results are expected for mutagenesis resulting from apyrimidinic sites. However, the mutation frequency for bleomycin-damaged phage was the same whether the phage were grown in a wild-type strain or in strains deficient in apurinic/apyrimidinic repair endonucleases; this was true even for an nth-nfo-xth- strain lacking all three major apurinic/apyrimidinic endonucleases (endonuclease III, endonuclease IV, and exonuclease III). Likewise, phage grown in an endonuclease IV-overproducing strain showed the same mutation frequency as those grown in wild-type cells. These data suggest that either i) bleomycin-induced mutagenesis results from SOS-dependent bypass of lesions other than apyrimidinic sites or ii) the number of apyrimidinic sites available for SOS processing is virtually independent of the level of apurinic/apyrimidinic endonuclease activity in the cell. It is possible that a fraction of the apyrimidinic sites induced by bleomycin either are intrinsically resistant to repair or undergo secondary reactions that render them resistant.

Bacterial Proteins↗
PubMed1989

Ultraviolet mutagenesis and the SOS response in Escherichia coli: a personal perspective.

The study of ultraviolet (UV) mutagenesis in Escherichia coli began with the assumption that genes were likely to be changed at the instant of photon absorption. Over many decades, it became clear that postirradiation cellular activities, including enzymatic DNA repair of UV photo products and error-prone modes of tolerating unrepaired DNA lesions can exert profound influences on the mutagenic outcome of irradiation. Current study focusses on the molecular details of radiation-induced translesion DNA replication as the final event in UV mutagenesis.

DNA Repair↗
PubMed1990

Comparison of the Salmonella (Ames) test, umu tests, and the SOS Chromotests for detecting genotoxins.

The limits of detection of 10 genotoxins representing 7 chemical classes with varying structures and modes of action were compared using the Ames test (Salmonella plate-incorporation test) with 2 tester strains, 2 standard colorimetric methods (the umu test and SOS Chromotest), and modifications of the umu and SOS Chromotests developed during the course of this study. The purpose of the study was to determine the sensitivity and reproducibility of each of the six methods. The sensitivities of the methods were compared using two criteria: the concentrations required for doubling responses, and the minimum concentrations required to produce statistically significant increases from background controls. The Ames test with strains TA98 and TA100 was ranked as the most sensitive method more often than the others, but the results indicated that the umu tests were statistically equivalent to the Ames test. The original SOS Chromotest kit method was highly sensitive in detecting the direct acting genotoxins, but neither SOS test was as sensitive as the other methods in detecting indirect acting genotoxins. The umu microtiter plate test is the least expensive of the assays and would be the most suitable for screening large numbers of environmental samples.

Animals↗
PubMed1991

Evaluation of the SOS chromotest for the detection of antimutagens.

The SOS chromotest was applied for the detection of antimutagens. To raise SOS induction, the bacteria were treated with the mutagens, UV, 4-nitroquinoline N-oxide (4NQO), N-methyl-N'-nitro-N-nitroso-guanidine (MNNG), or benzo[a]pyrene (B[a]p). The inhibitory effects of L-ascorbic acid, glutathione, vanillin, 5-fluorouracil (5-FU), 5-chlorouracil (5-CU), cobaltous chloride, sodium selenite and sodium arsenite, which are known as antimutagens, were investigated with their addition either simultaneously or post treatment time. It became clear that the SOS chromotest was very useful for the detection of antimutagens.

Ascorbic Acid↗
PubMed1991

Genotoxicity of nitrated polycyclic aromatic hydrocarbons and related structures on Escherichia coli PQ37 (SOS chromotest).

To determine the genotoxicity of nitrated polycyclic aromatic hydrocarbons and related molecules (nPAH) we examined 24 compounds representative of nitroanthracenes, nitrofluorenes, nitronaphthalenes, nitropyrenes, and nitroquinolines for genotoxicity in Escherichia coli PQ37 (SOS-chromotest). To enhance the sensitivity of the tester strain and optimize metabolic activation we used a modified test protocol and S9-mix composition. All chemicals with the exception of 9-nitroanthracene, 1- and 2-nitronaphthalene, 2-methyl-1-nitronaphthalene, and 5-, 6-, and 8-nitroquinoline induced the SOS system of E. coli PQ37. As expected from previously referred mutagenicity studies, the highest SOS inducing potencies (SOSIP) were exhibited by the dinitropyrenes (SOSIP = 151-416), 4-nitroquinoline-N-oxide (SOSIP = 62), and 3-nitrofluoranthese (SOSIP = 16). Except for some nitronaphthalenes, the nPAHs showed their highest genotoxicity in the absence of an exogeneous metabolic activation system. The results were compared to those reported for the bacterial mutagenicity of these substances in Salmonella typhimurium TA98.

Escherichia coli↗
PubMed1992

Evaluation of the mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives by the Ames test and the SOS chromotest.

The mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives have been evaluated by using modified versions of the Ames test and the SOS Chromotest. Salmonella typhimurium tester strain TA 100 was used with and without metabolic activation in the Ames test and Escherichia coli tester Strain PQ 37 was used with and without metabolic activation in the SOS Chromotest. Including metronidazole and dimetridazole, 45 derivatives were mutagenic and genotoxic. The mutagenic potencies (MP) ranged from 0.127 to 53,717 revertants/nmol while the SOS induction powers (SOSIP) ranged from 0.00131 to 107 IF/nmol. The overall correlation between MP and SOSIP was r = 0.845 (n = 84) as calculated by linear regression analysis. A higher correlation was observed between MP and SOSIP without the S9 mix than with it. Among the imidazole derivatives, the 5-nitroimidazoles with a lactam ring at the 2-position showed the highest MP and SOSIP. The presence of a nitro group at the 5-position was critical for the mutagenicity and the genotoxicity of the derivatives. Substituents at the 1- and 2-positions were also found to modulate these activities.

Animals↗