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Biomedical subjects

B A Bridges

Publications and source records attributed to B A Bridges.

At least 109 records · Page 6Linked to original sources
PubMed1982

The mutagenic potency of 1,8-dinitropyrene in cultured mouse lymphoma cells.

Although non-toxic, 1,8-dinitropyrene (1,8-DNP) was mutagenic for mouse lymphoma L5178Y cell when assayed for induced resistance to 6-thioguanine, methotrexate, ouabain and 1-beta-D-arabinofuranosyl cytosine. In bacteria, nitropyrenes are potent inducers of frame-shift mutations, and the induction of ouabain-resistant mutants, believed to be due to base-pair substitutions, suggests that the mechanism of action may be different in mouse cells and bacteria. Long treatment time were required to detect 1.8-DNP-induced mutants in L5178Y cells, suggesting the possibility of an inducible activation system. 4-Nitroquinoline 1-oxide was both toxic and mutagenic to these same 4 mutation assays after short (2h) treatment times. The dilemma that exists when comparing the mutagenic potential of test chemicals when concentration of mutagen, treatment times and toxicity are markedly different, is discussed.

4-Nitroquinoline-1-oxide↗
PubMed1981

Influence of mutations at the rep gene on survival of Escherichia coli following ultraviolet light irradiation or 8-methoxypsoralen photosensitization: evidence for a recA+ rep+-dependent pathway for repair of DNA crosslinks.

Bacteria mutant at the rep gene (specifying a DNA-unwinding enzyme) were slightly more sensitive than rep+ bacteria to far ultraviolet light (ca. 254 nm; (FUV) and to monofunctional psoralen photoproducts produced with near ultraviolet light (ca. 360 nm; NUV). The enhanced sensitivity was shown in uvrA excision-deficient bacteria but not in those carrying the recA mutation. It is concluded that the rep unwinding enzyme has a small promoting effect on post-replication recombination repair. Rep- bacteria were rather more sensitive to the DNA cross-linking action f 8-methoxypsoralen (8-MOP) and NUV. This effect also was found in uvrA but not in recA bacteria. A cross-link repair pathway, dependent on both the recA+ and rep+ genes, therefore exists in addition to the pathway which depends upon the uvrAB endonuclease. Various lines of evidence suggest that the pathway operates at or after DNA replication. Exposure of rep+ bacteria to 8-MOP plus NUV did not induce any activity capable of repairing psoralen cross-links in infecting lambda phage. A possible model involving removal of the cross-link by glycosylase action at the replication fork is proposed.

DNA Helicases↗
PubMed1981

Studies on the genotoxicity of some fluorescein dyes.

The activities of 2,4,5,7-tetraiodofluorescein, disodium salt (erythrosine) and 2 phloxine dyes (2,4,5,7-tetrabromo-12,15-dichlorofluorescein, dipotassium salt and the disodium salt of 2,4,5,7-tetraiodo-12,15-dichlorofluorescein) have been determined using DNA-repair, fluctuation and treat-and-plate assays. Tests were conducted with and without illumination from a daylight fluorescent lamp. Both phloxine dyes were active in a rec assay but only in the absence of a rat-liver microsomal metabolising system. Erythrosine was inactive under all conditions. Although the results agreed with some of the published data for these foods and cosmetic colours, previous reports of photodynamic activation and mutagenicity were not confirmed. In the light of recent concern over the efficacy of bacterial DNA-repair tests, it is considered that the results obtained are not at present conclusive evidence for genotoxic hazard of any of the dyes studied.

Eosine I Bluish↗
PubMed1981

Effect of gyrB-mediated changes in chromosome structure on killing of Escherichia coli by ultraviolet light: experiments with strains differing in deoxyribonucleic acid repair capacity.

Mutations at the gyrB locus were found to decrease the degree of supercoiling of the Escherichia coli chromosome. The effect of a gyrB mutation on the repair of ultraviolet-induced deoxyribonucleic acid damage was studied by following the killing of strains of E. coli K-12 proficient and deficient in deoxyribonucleic acid repair. The effectiveness of both excision and postreplication types of deoxyribonucleic acid repair was found to be altered by this mutation, the former being apparently enhanced and the latter impaired.

Chromosomes, Bacterial↗
PubMed1980

Inhibition of delayed hypersensitivity reaction in skin (DNCB test) by 8-methoxypsoralen photochemotherapy. Possible basis for pseudo-promoting action in skin carcinogenesis?

Fifty-five of a hundred and two subjects undergoing photochemotherapy with 8-methoxypsoralen and near ultraviolet showed an abnormally low or undetectable delayed cellular hypersensitivity reaction in the skin as judged by the dinitrochlorobenzene test. It is suggested that photochemotherapy may act as a pseudo-promotor by blocking an immunologically based control process in the skin so allowing the relatively rapid appearance of squamous skin tumours, documented elsewhere, in individuals whose skin already contains a population of potentially tumorous cells. Immune surveillance of a kind may thus operate in human skin. Impairment of delayed cellular hypersensitivity to dinitrochlorobenzene was more likely to occur with more intensive treatments and in patients with less skin pigmentation.

Adolescent↗
PubMed1980

Induction of enzymes involved in DNA repair and mutagenesis.

Three phenomena examined here have been claimed to reflect the operation of inducible repair systems. It has been postulated that 'SOS repair' involves the induction by DNA-damaging agents of an error-prone repair system that is capable of affecting the replication of damaged DNA. This system works with bacteriophages and animal viruses, in which it is possible to separate the effects of DNA damage on the viral DNA from that on the host cell. Whether this system also operates in repair of the cell's own DNA is, however, controversial. The system appears to have little effect on survival of bacterial cells and its operation in cellular mutagenesis is still not proven, at least in bacteria with otherwise normal repair capacity. 'Adaptation' is the response of bacteria to low doses of methylating agents. Adapted bacteria are more resistant to the lethal and mutagenic action of alkytlating agents. The process includes the induction of an enzyme that 'removes' O6-alkylated bases from DNA and which, unusually, is consumed during the course of the reaction. The reaction itself is also unknown; it does not depend on a nuclease, glycosylase or demethylase, but could use a transmethylase. There is some evidence that an analogous process occurs in animals. The third process affects the synthesis of high molecular weight DNA in cultured mammalian cells that have been exposed to split doses of DNA-damaging agents. It has been postulated that this system is inducible and error-free, but detailed analysis suggests that the observed effect is an artifact arising from an abnormal distribution of sizes of nascent DNA after the second dose, and as a result of exposure to the first dose. Inducible DNA repair systems may be expected to influence kinetics of the dose--response relationships obtained after exposure of cells to mutagens and carcinogens. The interactions between these effects and those produced by inducible pathways of metabolic activation and detoxification are discussed.

Alkylating Agents↗
PubMed1980

The fluctuation test.

The fluctuation test is an assay for the detection of mutation induction in bacteria by chemicals, carried out in liquid medium, and scored by counting the number out of around 50 tubes or wells that turn yellow. It is suitable for the Ames Salmonella strains or for Escherichia coli WP2 trp and its derivatives. Calcium precipitated microsomes, S9 fraction or freshly prepared hepatocytes can be incorporated for metabolic activation. It is comparable to the Ames test in its ability to detect mutagens and carcinogens and generally shares the limitations of that test as regards extrapolation to animals and man. Its disadvantages are that it is marginally slower and slightly more labour intensive than the Ames protocol. For certain applications, however, these disadvantages may be offset by the advantages of somewhat greater sensitivity, ability to be automated, and facility for using hepatocytes for metabolic activation. The test is particularly suitable for the testing of aqueous samples containing low levels of mutagen.

Bacteria↗
PubMed1980

Effect of tif expression, irradiation of recipient and presence of plasmid pKM101 on recovery of a marker from a donor exposed to ultraviolet light prior to conjugation.

To detect the effect of the postulated inducible error-prone repair system ('SOS repair') on the bacterial chromosome, an Hfr Escherichia coli strain JC5088 recA was u.v.-irradiated immediately before mating it with recipients in which SOS repair was supposed to be functioning through tif expression, u.v. irradiation or the presence of plasmid pKM101. The recombinant yields of these crosses were compared with those obtained in corresponding crosses with recipients in which SOS repair either was not induced or was totally eliminated by the lexA mutation. No difference in marker recovery efficiency could be detected between these two sets of recipients and thus no induced repair process acting on donor DNA could be demonstrated. The possible reasons for this finding are discussed.

Chromosomes, Bacterial↗
PubMed1979

Assays for the fidelity of DNA polymerases in cell-free extracts of Escherichia coli are complicated by contaminating nucleoside triphosphatases.

In the presence of DNA and a divalent cation, an enzyme activity in cell-free extracts of Escherichia coli readily hydrolyses dATP to dADP. dGTP is degraded to a smaller extent, dCTP and dTTP being hardly affected. The artificial template primers poly(dC) . oligo(dG) and poly(dT) . oligo(dA) are also effective cofactors for this triphosphatase activity. As a consequence, assays measuring the misincorporation, by cell-free extracts, of dATP and dGTP into these defined templates are difficult to interpret, since the triphosphate substrate is being rapidly degraded during the polymerase reaction. A partial characterization of the dATPase activity was performed, demonstrating that the optimal conditions for its activity resemble those commonly used for assaying polymerase activity. Thus in crude extracts both polymerase and dATPase compete for the same substrate. The inclusion of an ATP-generating system in the reaction mixture maintains the levels of deoxynucleoside triphosphates and changes the kinetics of misincorporation of dAMP into poly(dC) . oligo(dG). No reproducible difference in such misincorporation has been found between lysates prepared from tif-1 cells grown at either permissive or restrictive temperature.

DNA-Directed DNA Polymerase↗
PubMed1979

An estimate of genetic risk from 8-methoxypsoralen photochemotherapy.

A method based on a combination of cell culture and pharmacokinetic data is explored as a way of estimating the possible genetic risk to man from a mutagenic chemical. 8-methoxypsoralen, which is given to psoriasis patients as part of a photochemotherapy regime, is used, since it represents a 'real-life' situation and possesses properties that make it particularly amenable to this approach. It is concluded that treatment of males for a mean period of 10 years before their spermatozoa were involved in conception would increase the gene mutation rate in the male germ line by a factor of 0.00125. The implications of this for the incidence of sex-linked and dominant disease in man are elaborated and the assumptions and limitations are set out. The fragility of the estimates is emphasized.

DNA↗