Point Mutation Rate Research Articles

Somatic Cells as Indicators of Germinal Mutations in the Mouse

In attempts to find a prescreen for mutagens that may induce heritable mutations in mammals, an in vivo somatic mutation test has been developed in the mouse that uses a localized gene product (hair pigment), is relatively fast and cheap, and gives results that have some predictive value for point mutation induction in spermatogonia. Embryos heterozygous at specific coat color loci are exposed to the presumptive mutagen, and 3 weeks later the fur is observed for spots of altered color. It is possible to distinguish spots resulting from expression of the recessive (RS's) from spots having various other causes. In tests with seven compounds, mutation rates per locus and unit dose have been calculated on the assumption that 175 cells are at risk per 10¼-day embryo (a number derived from distribution of spot proportions). These rates are found to be roughly parallel to, but uniformly higher than spermatogonial point-mutation rates for the same seven compounds. The higher somatic rates are presumably due to the fact that RS's can result from several genetic mechanisms besides point mutations. The spot test, which has not to date given any false negatives, may thus be considered a useful in vivo prescreen for heritable germinal mutations in mammals.

Somatic cells as indicators of germinal mutations in the mouse

In attempts to find a prescreen for mutagens that may induce heritable mutations in mammals, an in vivo somatic mutation test has been developed in the mouse that uses a localized gene product (hair pigment), is relatively fast and cheap, and gives results that have some predictive value for point mutation induction in spermatogonia. Embryos heterozygous at specific coat color loci are exposed to the presumptive mutagen, and 3 weeks later the fur is observed for spots of altered color. It is possible to distinguish spots resulting from expression of the recessive (RS's) from spots having various other causes.In tests with seven compounds, mutation rates per locus and unit dose have been calculated on the assumption that 175 cells are at risk per 10(1/4)-day embryo (a number derived from distribution of spot proportions). These rates are found to be roughly parallel to, but uniformly higher than spermatogonial point-mutation rates for the same seven compounds. The higher somatic rates are presumably due to the fact that RS's can result from several genetic mechanisms besides point mutations. The spot test, which has not to date given any false negatives, may thus be considered a useful in vivo prescreen for heritable germinal mutations in mammals.

Isolation and characterization of mutants of the plasmid pKM101 deficient in their ability to enhance mutagenesis and repair

A screening procedure was developed for identifying mutants of the plasmid pKM101 no longer capable of enhancing mutagenesis. The test was based on the large pKM101-mediated increase in the number of Gal+ papillae observed on colonies of Salmonella typhimurium gal mutants plated on tetrazolium-galactose plates in the presence of a mutagen. The pKM101 mutant plasmids transferred normally, were stably maintained in cells, caused normal levels of ampicillin resistance, and still imparted sensitivity to phage Ike to their hosts. However, the pKM101 mutants had lost the ability to (i) enhance the reversion of both point and frameshift mutations, (ii) protect the cells against killing by UV irradiation, (iii) increase the spontaneous reversion rates of point mutations, (iv) enhance plasmid-mediated reactivation of UV-irradiated phage P22, (v) enhance Weigle reactivation. One pKM101 mutant with different properties from the others was identified by its increased spontaneous mutator effect. It is suggested that pKM101 amplifies the activity of the inducible error-prone repair systems in bacteria and that this is the function of pKM101 in the Ames Salmonella tester strains used for detection of carcinogens as mutagens.

Gamma-ray mutagenesis in bacteriophage T4.

137Cs-gamma irradiation of bacteriophage T4 induces large deletions plus a variety of types of point mutations. All mutations arise with single-hit kinetics, and all by a misrepair process. The estimated point mutation rate is 1.5 X 10(-9) per locus per rad.

Comparison of point mutation rates in different species with human mutation rates.

Comparison of point mutation rates in different species with human mutation rates.

A Relationship between Spontaneous and Radiation-Induced Loss of Specific Molecular Structure

The energy distribution of a radiation field of discrete high-energy events can be compared with the Boltzmann distribution in regard to effectiveness in producing biomolecular transitions. This comparison provides an absolute relationship between the rates of radiation-induced and spontaneous biomolecular transitions. Such a relationship allows the calculation, on purely theoretical grounds, of the radiation dose rate which doubles the spontaneous rate of point mutations.

PATTERNS OF SPONTANEOUS AND RADIATION INDUCED MUTATION RATES DURING SPERMATOGENESIS IN DROSOPHILA MELANOGASTER.

The daily pattern of mutational response to gamma rays was determined for three types of young adult, heterozygous, Oregon-R males which were mated exhaustively during days 1 to 12 after irradiation. Doses of 250r, 500r, and 1kr were tested for the production of dominant visible and sex-linked hemizygous mutations, and 1kr for Y and autosomal translocations. Translocations were also scored in tests of irradiated mature sperm, and of sperm maturing five to six days later, after doses of 250r, 500r, 2kr and 4kr. The observed pattern was that of an even rate for the visibles, chiefly Minutes, and was U-shaped for sex- linked mutations, chiefiy lethals, with the lower rate appearing in sperm from days 2 to 8. A linear relationship with dose is indicated for the rates of all types of induced point mutations in sperin from days 1 to 8. In premeiotic stages of spermatogenesis the relationship varies between dosage levels and between the types of heterozygous males tested. Sperin derived from gonial cells which did not mutate at the ttme of exposure to doses of 1kr to 5kr showed that the same rate of spontaneous mutations occurred in subsequent stages of spermatogenesis as occurred in the spermmore » of similarly aged Control males. After 1kr, day-5 sperm showed 3.7 times more sex-linked mutations than appeared in sperm from days 1 to 3, and day-8 sperm showed 11.8 times more translocations. This favors the view that changes in mutation frequency during days 1 to 6 reflect changes in the rate at which both point mutations and chromosome rearrangements occur during the various stages of spermatogenesis from ineiosis to maturity. The rate of translocations increases at approximately the 1.8 power of the increase in dose in both mature sperm and sperre maturing five to six days after irradiation, and the rate of point mutations increases linearly at both of those times. This supports the view that the mutation process does not change during the meiosis-to- maturation period of spermatogenesis. At the time of peak response in meiosisspermiogenesis, as well as in mature sperm, after 250r to 1kr, dominant visibles appear to be a mixture of point and position-effect mutations. Increasing the time required for development by lowering the temperature increases proportionately the number of days to the peak mutational response in irradiated sperm. This favors the interpretation that peak mutation rates are associated with specific stages in spermatogenesis. (auth)« less