The effect of repeated microwave irradiation on the frequency of sex-linked recessive lethal mutations in Drosophila melanogaster

The effect of repeated microwave irradiation (2375 MHz, CW) on mutagenic changes in Drosophila melanogaster was investigated. Oregon-R males were exposed to sublethal doses of microwaves (15 W/cm2 for 60 min, 20 W/cm2 for 10 min, and 25 W/cm2 for 5 min) for 5 days. The Muller-5 cross was used to detect sex-linked recessive lethal mutations. 4 lethals were found in treated groups but their frequency was not significantly different from that of the control group. No cumulative effect of repeated exposures on the mortality of the treated males was observed; on the contrary, their mortality decreased with the number of exposures. Irradiation did not affect the sex ratio of the F1. A significant decrease in the number of F1 offspring was noted in the group exposed to the power density of 15 W/cm2. A negative thermal effect of microwaves on male germ cells was probably manifested by this long exposure.     

Temperature-sensitive autosomal dominant lethal mutations in Drosophila melanogaster induced by ethylmethane sulfonate

Cold- and heat-sensitive dominant autosome and recessive sex-linked lethals were scored using C(1)RM, y; vg bw; e ss tester stock. The frequencies of heat-sensitive mutations were 1.43, 0.30, 0.07% and of cold-sensitive ones were 0.39, 0.16 and 0.09% in the 1-st, 2-nd and 3-rd chromosomes, respectively. For the first time, dominant cold-sensitive lethals were obtained in chromosome 3. The data from genetic analysis point to the fact that penetrance of such mutations strongly depends on the genetic background. That may be the reason, why they were not obtained using some of the balancer-3 chromosomes. Also, "cryptic" dominant autosome mutants were found which were not conditional but only revealed in the F2 generation. Their possible origin as gonado-somatic mosaics is discussed.     

The level of dysgenic sterility and recessive mutations induced in laboratory strains of Drosophila melanogaster exposed to chronic low-dose gamma irradiation

Recent investigations showed that genetic instability accounts for many radiobiological effects. However, mechanisms underlying this phenomenon are still poorly understood. Assuming that mobile genetic elements may be involved in the induction of genetic instability, we studied parameters that characterize the activity of these elements in Drosophila melanogaster: hybrid dysgenesis and the level of recessive lethal mutations. In our experiments, we used D. melanogaster strains that differed in the type of hybrid dysgenesis (P-M and H-E). It was demonstrated that chronic exposure to radiation leads to substantial changes in the genetic structure of a population and an enhanced level of dysgenic sterility. Our results indicate that genetic instability and adaptation to the effect of chronic gamma-radiation are associated with the radiation-induced mobilization of mobile genetic elements.     

Genetic analysis of recessive lethal mutations induced by the influenza virus in the X chromosome of Drosophila melanogaster

Mutagenic potential of the influenza virus was evaluated. Based on its capacity of inducing recessive lethal mutations in the X chromosome of Drosophila melanogaster, the influenza virus can be classified as a moderate-activity mutagen. Its mutagenicity does not depend on ability to reproduce in the cell system. This virus was shown to disrupt formation of the wing, particularly wing vein M1 + 2. Cytogenetic examination of polytene X chromosomes bearing recessive lethal mutations in Drosophila salivary glands did not reveal chromosome rearrangements. These lethals are assumed to be small deletions or point mutations. The determination of the lethal activity stage of these mutations showed that they disrupt the expression of genes functioning at various developmental stage of Drosophila. Two of them were conditionally lethal (temperature-sensitive). Two of 15 mutations analyzed were mapped to region 2B9-10-3C10-11.     

Autosomal recessive lethal mutations in two mutator stocks of Drosophila ananassae.

The frequency of recessive lethals in the 2nd chromosome was examined in two mutator stocks of Drosophila ananassae, ca and ca; px. They are characterized respectively by possessing an extrachromosomal clastogenic mutator in males, and by the retrotransposon "tom", which induces Om mutability only in females. The frequencies of recessive lethal mutations in the 2nd chromosome among progenies from males and females of the ca; px stock are 0.35 and 0.34 percent, respectively. Similarity of these frequencies indicates that tom does not induce recessive lethals in females. In contrast to the ca; px stock, the frequency of recessive lethals in males of the ca mutator stock was estimated to be 1.54 percent for the 2nd chromosome. No visible mutants except Minutes were recovered. Some recessive lethals derived from ca stock males were associated with chromosomal rearrangements. Being consistent with its high rate of Minute mutation it was demonstrated that the ca clastogenic mutator also induced recessive lethals.     

Studies on the induction of sex-linked recessive lethal mutations in Drosophila melanogaster by nitroheterocyclic compounds

24 nitroheterocyclic compounds were investigated for their capacity to induce sex-linked recessive lethals in Drosophila, by the adult feeding technique, and in some cases injection or larval-feeding methods. Out of 9 5-nitroimidazoles, ZK 26.173 and ZK 25.095 (moxnidazole) were clearly active whereas nimorazole and ronidazole were marginally mutagenic. Out of 10 5-nitrofurans, nitrovin, furazolidone and furaltadone were unambiguously mutagenic, whereas nitrofurantoin was a borderline case. Nitrofurans were active at lower molar concentrations than nitroimidazoles. Out of a group of 5 related nitro compounds (2 nitrothiophenes, picrolonic acid, niridazole and 4-NQO), only 4-NQO was clearly mutagenic, when fed to larvae. Experiments with germ-free flies showed that, for ZK 26.173 and furazolidone, the gut flora of Drosophila do not play a role in the activation of the compounds to mutagenic metabolites. Furazolidone, 4-NAO, ZK 26.173, ZK 25.095 and furaltadone were tested in mal and cin strains, both of which lack xanthine dehydrogenase and aldehyde oxidase. The latter enzyme and xanthine oxidase are known to carry out nitro reduction in mammalian tissues. For ZK 26.173, the mutation frequencies were drastically reduced in the enzyme-deficient strains, indicating the involvement of one of these enzymes in the activation of this substance.     

The maternal effect of lethal(1)discs-large-1: a recessive oncogene of Drosophila melanogaster

The maternal effect phenotypes of recessive mutations at the Drosophila zygotic lethal gene l(1)discs-large-1 (l(1)dlg-1) are described. L(1)dlg-1 is located in 10B7-8 on the salivary gland chromosome map. A complex complementation pattern is observed among the nine characterized alleles. Larvae missing zygotic l(1)dlg-1+ gene activity die due to aberrant growth of imaginal cells at the larval-pupal transition. Embryos lacking both maternal and zygotic activity of l(1)dlg-1+, i.e., embryos derived from homozygous l(1)dlg-1 germ line clones for null alleles, show neurogenesis and morphogenesis defects that result in very abnormal embryos. Although differentiated, most tissues are morphologically misshapen. This maternal effect is rescuable to some extent. One allele, l(1)dlg-1HF321, is a temperature-sensitive mutation for the zygotic lethality. Embryos derived from homozygous l(1)dlg-1HF321 females at 18 degrees C exhibit defects associated with dorsal closure and head involution. More extreme phenotypes are observed when females are shifted to higher temperatures and include defective dorsal closure, collapse of the somatic musculature, and an oversized central nervous system. The possible involvement of the recessive oncogene l(1)dlg-1 in cell adhesion is discussed.     

Increment kinetics of recessive lethal mutations and dominant lethals in offspring of Drosophila melanogaster on storage of methyl-methanesulfonate-treated sperm in females

The frequencies of sex-linked recessive lethal mutations in F1 males after feeding adult male Drosophila melanogaster with 0.25 and 0.5 mM methyl methanesulfonate (MMS) orally for 24 h increased approximately linearly with storage of the treated spermatozoa in females, whereas the number of hits of dominant lethals in the sperm after feeding 0.3 and 0.5 mM MMS increased approximately with the square of the storage time. Chromosome losses and mosaics in F1 males also increased with the dose of MMS to males, but their yields were too low to be analyzed quantitatively, only indicating a slight increase of chromosome loses and a slight decrease of mosaics with the time of storage of sperm. Maternal non-disjunctions (or chromosome losses), detected in F1 males, decreased with the dose of MMS to spermatozoa and their yield decreased with the time of storage of sperm of both MMS-treated and the control groups. A unitary model is proposed to explain the effect of storage on the dominant lethals and recessive lethal mutations.     

The dominant lethal effect of dietary triethylenemelamine.

Triethylenemelamine (TEM) was administered in the diet to adult male mice at doses of 0.1, 0.3, 1, 10 or 50 mg/kg body weight for 45 days or at doses of 0.1 or 0.3 mg/kg b.w. for 10 days. As a comparison, male mice were treated intraperitoneally with 5 daily doses of 0.25 or 0.5 mg TEM/kg b.w. At the end of the treatment period, males were mated sequentially with 2 untreated virgin females each for 2 or 3 weeks. Near mid-pregnancy the number of implantation sites and fetal deaths were determined. TEM, administered in the diet at 10 or 50 mg/kg b.w. for 45 dyas, was lethal to male mice. Surviving males from the 1 mg/kg level failed to impregnate any females during the two matings. TEM, given in the diet at 0.1 or 0.3 mg/kg for 10 or 45 dyas, decreased fertility and increased dominant lethal mutations in a dose and time dependent manner. These results were comparable to those obtained from males treated i.p. with TEM at 0.25 or 0.5 mg/kg b.w.     

Non-random distribution of spontaneous and high temperature-induced recessive lethal mutations in the X-chromosome of Drosophila]

Frequency and localization of spontaneous and induced by high temperature (37 degrees C) recessive lethal mutations in X-chromosome of females belonging to the 1(1) ts 403 strain defective in synthesis of heat-shock proteins (HSP) were studied. No differences in frequencies of both spontaneous and induced lethals between 1(1) ts 403 and control strain were found, thus implying that the disturbances in HSP synthesis have no effect on this process in oocytes of Drosophila melanogaster females. Surprisingly, distribution of spontaneous and induced lethals along the X-chromosome of 1(1) ts 403 strain appeared to be non-random: they primarily are located in its distal portion (1-44 cM of genetic map or in I-II sections of the Bridges cytogenetic map). This correlates with non-random distribution of mobile elements in the X-chromosome of D. melanogaster (Leibovich, 1990).     

The induction of dominant lethal mutations in Tilapia mossambica by alkane sulphonic esters.

A serial mating system has been used to enable study of the effect of chemical mutagens in Tilapia mossambica. Embryopathies incompatible with survival are attributed to dominant lethal mutations induced in developing male germ cells by methyl methanesulphonate and the isomeric forms of dimethyl-myleran.     

The effects of recessive lethal Notch mutations of Drosophila melanogaster on flavoprotein enzyme activities whose inhibitions cause Notch-like phenocopies

The biochemical action of the Notch locus whose mutants cause morphological aberrations in flies, viz., notches of wings and bristle multiplication, has been analyzed (1) by the addition to the food medium of enzyme inhibitors causing phenocopies of Notch and (2) by comparison of enzyme activity patterns of Notch mutants with different degrees of phenotypic expression. Notch phenocopies were induced by inhibitors of enzyme activities in two biochemical pathways: (1) the de novo pyrimidine synthesis by 5-methylorotate (inhibitor of dihydroorotate dehydrogenase) and (2) the choline shunt by amobarbital (inhibits choline dehydrogenase) and methoxyacetate (inhibits sarcosine dehydrogenase). The inhibition of de novo pyrimidine synthesis prevents the production of deoxyuridine-5-phosphate, the substrate for the synthesis of thymidine-5-phosphate via thymidylate synthase, whereas the inhibition of the choline shunt prevents the production of HCHO groups and glycine, both of which are involved in the synthesis of 5,10-methylenetetrahydrofolate, which is a cofactor of thymidylate synthase. It was already known that the inhibition of the latter enzyme in vivo induces Notch phenocopies. Notch mutants with a strong morphological expression show low enzyme activities for dihydroorotate dehydrogenase and choline dehydrogenase. Both are flavoprotein enzymes linked to the respiratory chain. The correspondence between the low enzyme activities in Notch mutants with a strong morphological expression and the phenocopying effect of antimetabolites on these enzymes in the two biochemical pathways involved strongly suggests that the morphological effects of Notch on flies are a consequence of lowered activities of choline dehydrogenase and dihydroorotate dehydrogenase.     

X-ray induced dominant lethal mutations in mature and immature oocytes of guinea-pigs and golden hamsters.

The induction of dominant lethal mutations by doses of 100-400 rad X-rays in oocytes of the guinea-pig and golden hamster was studied using criteria of embryonic mortality. For both species higher yields were obtained from mature than from immature oocytes, in contrast to results for the mouse. Data on fertility indicated that in the golden hamster, as in the mouse, immature oocytes were more sensitive to killing by X-rays than mature oocytes but that the converse was true in the guinea-pig. The dose-response relationship for mutation to dominant lethals in pre-ovulatory oocytes of guinea-pig and golden hamsters was linear, both when based on pre- and post-implantation loss and when on post-implantation loss only. The rate per unit dose was higher for the golden hamster, and the old golden hamsters were possibly slightly more sensitive than young ones. The mutation rate data for mature oocytes of the mouse, using post-implantation loss alone, also fitted a linear dose-response relationship, except that the rate per unit dose was lower than for the other two species.