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D J Tweats

Publications and source records attributed to D J Tweats.

27 records · Page 2Linked to original sources
PubMed1982

Mutagen formation after the addition of nitrite to normal human gastric juice.

The World Health Organisation (WHO) has recently recommended the use of a simple in vitro test (Nitrosation Assay Procedure, NAP) to allow the ranking of orally administered drugs. It was suggested that the ranking of drugs should be carried out on a reactivity scale, according to their ability to nitrosate in the presence of high concentrations of nitrite at low pH (3-4). The present study was undertaken to investigate the effect of adding the concentration of nitrite recommended for the NAP Test (40 mM) to normal fasting human gastric juice. The data clearly demonstrate that such treatment results in the formation of derivatives with specific mutagenic activity for the bacterium Salmonella typhimurium TA1537. This strain was recommended for use in the NAP Test. Although the NAP Test may be valid for its original purpose, in the absence of more physiologically relevant data it is invalid for use as a final arbiter in risk-benefit assessments. The possible formation of mutagenic species as a result of the nitrosation of natural gastric secretions should be considered when any risk-benefit assessment is made.

Amines↗
PubMed1981

A differential killing assay for mutagens and carcinogens based on an improved repair-deficient strain of Escherichia coli.

The lexA gene suppresses the spontaneous inviability of recA strains of Escherichia coli without affecting their repair deficiency. We have taken advantage of this to construct a uvrA recA lexA triple mutant CM871 that combines extreme repair deficiency with near wild-type growth. We have used this strain in conjunction with an isogenic strain WP67 uvrA polA and isogenic wild-type strain WP2 in a differential killing test. Dilute suspensions in buffer of the repair-deficient strains and repair-proficient control are incubated for 2 h at 37 degrees C with test compound in the presence or absence of a S9 metabolising system. Survival is determined by Miles Misra plating. For each strain three 10 microliter spots of each of three concentrations of test compound and of the untreated control are placed on a nutrient agar plate. Following overnight incubation survivors are counted. Results with reference compounds are given and the advantages and disadvantages of the test are discussed.

Animals↗
PubMed1976

R factor-mediated resistance to ultraviolet light in strains of Escherichia coli deficient in known repair functions.

The expression of resistance to u.v. irradiation mediated by R factor R46 has been studied in strains deficient in excision repair and recombination repair. The R factor protected wild-type bacteria and also wild-type cells in which repair had been inhibited by the substitution of bromouracil for chromosomal thymine. It increased the survival of strains defective in the endonucleolytic (uvr), repolymerizing (pol) and joining (lig) stages of the excision repair process. Recombination deficient bacteria mutant at the recB or recC loci were protected by R46, but the R factor had little effect on the survival of a recA strain or a recA recB double mutant. R46 increased the survival of cells that had been treated with chloramphenicol before u.v. irradiation, but did not protect cultures treated with chloramphenciol after irradiation. It is concluded that R46 confers resistance to the lethal effects of u.v. irradiation by a mechanism that is independent of excision repair. Resistance appears to be mediated by an inducible gene product, which is possibly a nuclease and dependent on a functional host recA gene for expression.

Bromodeoxyuridine↗
PubMed1974

R-factor-mediated nuclease activity involved in thymineless elimination.

R-factor 1818 (R-1818) had no effect on the efficiency of plating of ligase-deficient phage T4 mutants on strains of Escherichia coli containing excess, normal, or defective ligase. However, if the R(+) bacterial strain that overproduced ligase was first starved of thymine, its ability to propagate ligase-deficient phage was reduced by as much as fivefold compared with the burst size on the thymine-starved R(-) strain. In contrast, it was found that after ultraviolet irradiation of the host the phage burst size was higher on the R(+) ligase overproducing strain than the R(-) derivative. The maximal level of R-factor elimination produced by thymine starvation was inversely related to the ligase level of the host. Ultraviolet irradiation did not cure the R factor from strains containing wild-type levels of ligase, but did cause elimination from strains with excess or defective ligase. The results suggest that R-1818 codes for a nuclease that is induced by thymine starvation and which, possibly in conjunction with host-mediated nucleases, is responsible for its elimination under these conditions.

Anti-Bacterial Agents↗
PubMedDate not supplied

The predictive value of batteries of short-term tests for carcinogens.

Carcinogenesis is a multistage process in which many factors may affect the outcome. No single short-term test, measuring a single endpoint, can predict chemically induced carcinogenesis with infallibility. Therefore it is necessary to use a battery of tests when screening new compounds. Ideally, tests to be used in this way should be validated rigorously. Test batteries should not be used in isolation but should be complemented by information from studies of metabolism, pharmacokinetics, etc. Such an approach is proving valuable for the detection of carcinogens already present in the environment and for screening new chemicals for latent hazards.

Animals↗