Mutation Research 

About: Mutation Research is an academic journal published by Elsevier BV. The journal publishes majorly in the area(s): DNA damage & DNA repair. It has an ISSN identifier of 1383-5718. Over the lifetime, 11523 publications have been published receiving 492171 citations.

Methods for detecting carcinogens and mutagens with the salmonella/mammalian-microsome mutagenicity test

Abstract: We describe in this paper the general methods for using the Salmonella/microsome test as a mutagenesis screening system. The methods described include the standard plate test, the use and storage of the bacterial tester strains, preparation and use of the liver homogenates (S/sub 9/), and the methods of inducing the rats for elevated microsomal enzyme activity. The application of this test system to screening large numbers of compounds, and the interpretation of test results is also discussed.

Revised methods for the salmonella mutagenicity test

Abstract: The methods for detecting carcinogens and mutagens with the Salmonella mutagenicity test were described previously (Ames et al., 1975b). The present paper is a revision of the methods. Two new tester strains, a frameshift strain (TA97) and a strain carrying an ochre mutation on a multicopy plasmid (TA102), are added to the standard tester set. TA97 replaces TA1537. TA1535 and TA1538 are removed from the recommended set but can be retained at the option of the investigator. TA98 and TA100 are retained. We discuss other special purpose strains and present some minor changes in procedure, principally in the growth, storage, and preservation of the tester strains. Two substitutions are made in diagnostic mutagens to eliminate MNNG and 9-aminoacridine. Some test modifications are discussed.

The in vitro micronucleus technique.

Abstract: The study of DNA damage at the chromosome level is an essential part of genetic toxicology because chromosomal mutation is an important event in carcinogenesis. The micronucleus assays have emerged as one of the preferred methods for assessing chromosome damage because they enable both chromosome loss and chromosome breakage to be measured reliably. Because micronuclei can only be expressed in cells that complete nuclear division a special method was developed that identifies such cells by their binucleate appearance when blocked from performing cytokinesis by cytochalasin-B (Cyt-B), a microfilament-assembly inhibitor. The cytokinesis-block micronucleus (CBMN) assay allows better precision because the data obtained are not confounded by altered cell division kinetics caused by cytotoxicity of agents tested or sub-optimal cell culture conditions. The method is now applied to various cell types for population monitoring of genetic damage, screening of chemicals for genotoxic potential and for specific purposes such as the prediction of the radiosensitivity of tumours and the inter-individual variation in radiosensitivity. In its current basic form the CBMN assay can provide, using simple morphological criteria, the following measures of genotoxicity and cytotoxicity: chromosome breakage, chromosome loss, chromosome rearrangement (nucleoplasmic bridges), cell division inhibition, necrosis and apoptosis. The cytosine-arabinoside modification of the CBMN assay allows for measurement of excision repairable lesions. The use of molecular probes enables chromosome loss to be distinguished from chromosome breakage and importantly non-disjunction in non-micronucleated binucleated cells can be efficiently measured. The in vitro CBMN technique, therefore, provides multiple and complementary measures of genotoxicity and cytotoxicity which can be achieved with relative ease within one system. The basic principles and methods (including detailed scoring criteria for all the genotoxicity and cytotoxicity end-points) of the CBMN assay are described and areas for future development identified.

The relation of recombination to mutational advance.

Abstract: The method of calculation is shown wherebt a formula has been derived that approximately the ratio of the rate of accumulation of advantageous mutant genes in a population that undergoes recombination to the rate in an otherwise non-recombining one. A table is given showing the ratios thus found for different frequencies of advantageous mutations and different degrees of their advantage. It is shown that this calculation does not apply for mutant genes that act advantageously only when in some special combinations with one or more other mutant genes, and that as far as these cases of special synergism are concerned recombining lines have no evolutionary advantage over non-recombining ones. Other limitations of the formula are pointed out and assessed. It is explained that most factors that retard the rate of recombination—for expample, linkage, rarity of outbreeding, intercalation of sexual reproduction between more frequent cycles of sexual propagation, and partial isolation between subpopulations—must usually cause little long-term retardation of the speed of advance that is fostered by recombination. Moreover, even where long-term evolutions has virtually ceased, recombination of mutant genes still confers upon a population the means of adopting short-term genetic “dodges”, that adjust it to ecological and “physical” changes in its circumstances, much more rapidly than would be possible for a comparable asexual population. Under conditions where only stability of type is needed, a non-recombining does not actually degenerate as a result of an excess of mutation over selection, after the usual equilibrium between these pressures is reached. However, a irreversible ratchet mechanism exists in the non-recombining species (unlike the recombining ones) that prevents selection, even if intensified, from reducing the mutational loads below the lightest that were in existence when the intensified selection started, whereas, contrariwise, “drift”, and what might be called “selective noise” must allow occasional slips of the lightest loads in the direction of increased weight.