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R A Nilan

Publications and source records attributed to R A Nilan.

15 recordsLinked to original sources

Interaction of the mutagenic metabolite of sodium azide, synthesized in vitro, with DNA of barley embryos.

The in vitro synthesized sodium azide mutagenic metabolite (azidoalanine) produced single-strand breaks and proteinase K-sensitive sites in isolated, germinating barley embryos. In contrast with sodium azide, the efficiency of DNA damage induction was lower, and both types of DNA lesions were totally or partially repaired in the course of subsequent 24 h incubation of the embryos. The mutagenic azide metabolite did not inhibit DNA replication, while azide did so even at doses which are not highly mutagenic. The metabolite labelled with 14C at the amino acid residue was taken up with a similar efficiency both into barley embryos germinating for 2 days and into cells of Salmonella typhimurium TA100. The majority of the radioactivity was incorporated into proteins, less into RNA and a negligible amount into DNA.

Alanine

Synthesis and mutagenicity of the two stereoisomers of an azide metabolite (azidoalanine).

The L- and D-isomers of azidoalanine (azide metabolite) have been chemically synthesized with 60% yield using corresponding N-(tert-butoxycarbonyl)-serine as starting materials. The mutagenic properties of synthesized L-azidoalanine are very similar to those of azide and in vivo synthesized azidoalanine. Synthetic D-azidoalanine shows very low mutagenic activity on Salmonella typhimurium TA1530 strain compared to that of the L-isomer. Thus a stereoselective process is involved in azidoalanine mutagenicity. The data presented in this study suggest that further biochemical activation is required for L-azidoalanine to produce its mutagenic activity.

Alanine

A mutagenic metabolite synthesized by Salmonella typhimurium grown in the presence of azide is azidoalanine.

A mutagenic azide metabolite was purified from the medium in which Salmonella typhimurium cells were grown in the presence of azide. This metabolite was identified to be azidoalanine based on infrared and mass spectroscopy and elemental analysis. This compound appeared to be identical to the mutagenic compound synthesized in vitro from azide and O-acetylserine by partially purified O-acetylserine sulfhydrylase. The metabolite (azidoalanine) mutagenic efficiency and spectrum in S. typhimurium was similar to that of inorganic azide. The compounds 2-azidoethylamine, 2-bromoethylamine, 3-bromopropionic acid and N-(azidomethyl) phthalimide were also mutagenic with a similar spectrum to azide and azidoalanine, but with lower efficiency. The compounds 3-azidopropylamine, 4-azidobutylamine, 3-chloroalanine and ethylamine were only weakly or nonmutagenic. Numerous other chloro, bromo and azido phthalimide derivatives tested were nonmutagenic. It is suggested that the lack of azide mutagenicity (and perhaps carcinogenicity) in mammalian cells may be due to their inability to convert azide to azidoalanine.

Alanine

In vivo conversion of sodium azide to a stable mutagenic metabolite in Salmonella typhimurium.

Salmonella typhimurium TA1530 and G46 strains growing in minimal medium supplemented with sodium azide produce a stable mutagenic metabolite which is not azide. The production of this metabolite is restricted to the log phase of bacteria grown in the presence of azide. The metabolite is highly mutagenic in DNA-repair defective base-substitution strains TA1530 and TA1535, but ineffective in frameshift strains TA1538 and TA1537. The metabolite induces mutations in resting cells of the TA1530 strain.

Azides

Mutagenic and chromosome-breaking effects of azide in barley and human leukocytes.

Azide (10-3 M, solution buffered at pH 3) is more effective in inducing mutations in embryonic shoots of seeds germinated between 8 and 16 h than in non-germinated seeds and in seeds germinated between 0 and 8 h and 16 to 28 h. This peak of chlorophyll-deficient seedling mutation frequency coincides with maximum frequencies of seeding lethals and DNA replication in the cells of the embryonic shoot. The mutation data suggest azide may only act on replicating DNA. Azide induced no chromosome-aberration frequencies significantly above controls in (1) embryonic shoots of barley seeds germinated for 8--12 h, (2) microspores of barley and (3) human leukocytes. It appears to be a point-mutation mutagen.

Azides

Azide.

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Animals

Potential of plant genetic systems for monitoring and screening mutagens.

Plants have too long been ignored as useful screening and monitoring systems of environmental mutagens. However, there are about a dozen reliable, some even unique, plant genetic systems that can increase the scope and effectiveness of chemical and physical mutagen screening and monitoring procedures. Some of these should be included in the Tier II tests. Moreover, plants are the only systems now in use as monitors of genetic effects caused by polluted atmosphere and water and by pesticides. There are several major advantages of the plant test systems which relate to their reproductive nature, easy culture and growth habits that should be considered in mutagen screening and monitoring. In addition to these advantages, the major plant test systems exhibit numerous genetic and chromosome changes for determining the effects of mutagens. Some of these have not yet been detected in other nonmammalian and mammalian test systems, but probably occur in the human organism. Plants have played major roles in various aspects of mutagenesis research, primarily in mutagen screening (detection and verification of mutagenic activity), mutagen monitoring, and determining mutagen effects and mechanisms of mutagen action. They have played lesser roles in quantification of mutagenic activity and understanding the nature of induced mutations.Mutagen monitoring with plants, especially in situ on land or in water, will help determine potential genetic hazards of air and water pollutants and protect the genetic purity of crop plants and the purity of the food supply. The Tradescantia stamen-hair system is used in a mobile laboratory for determining the genetic effects of industrial and automobile pollution in a number of sites in the U.S.A. The fern is employed for monitoring genetic effects of water pollution in the Eastern states. The maize pollen system and certain weeds have monitored genetic effects of pesticides. Several other systems that have considerable value and should be developed and more widely used in mutagen monitoring and screening, especially for in situ monitoring, are discussed. Emphasis is placed on pollen systems in which changes in pollen structure, chemistry, and chromosomes can be scored for monitoring; and screening systems which can record low levels of genetic effects as well as provide information on the nature of induced mutations. THE VALUE OF PLANT SYSTEMS FOR MONITORING AND SCREENING MUTAGENS CAN BE IMPROVED BY: greater knowledge of plant cell processes at the molecular and ultrastructural levels; relating these processes to mutagen effects and plant cell responses; improving current systems for increased sensitivity, ease of detecting genetic and chromosome changes, recording of data (including automation), and for extending the range of genetic and chromosome end points; and designing and developing new systems with the aid of previous and current botanical and genetic knowledge.

Biological Assay

Artificial mutagenesis as an aid in overcoming genetic vulnerability of crop plants.

Artificially induced genetic variation is being used effectively to supplement or complement sources of natural origin for practical plant breeding. Thus, creating genetic variation uill become increasingly important as crop genetic resources become more difficult to obtain via plant exploration. The aritificial induction of useful genetic variation offers important elements that can be used for overcoming genetic vulnerability: (1) new, previously unknown alleles can be induced in crop plant species to broaden the base of variation; (2) useful genetic variation can be induced in modern cultivars helping to shorten breeding time or to extend production "life"; (3) characteristics of existing genetic resource stocks can be improved to make them more useful in breeding; and (4) recombination in crosses may be enhanced. The performance of induced mutant crop cultivars and the successful uses of induced genetic variation in cross breeding indicate that artificial mutagenesis will play an increasingly greater role in plant breeding.

Alleles