Repair-deficient Females Research Articles

Studies on mutagen sensitive strains of Drosophila melanogaster. XI. Survival (dominant lethality) after X-irradiation and relation to recessive lethals and translocations

Muller-5 males of Drosophila melanogaster were irradiated in N 2 or O 2 and mated to excision repair deficient, post-replication repair deficient ( mei-9 a, mei-41 D5, mus101 D1, mus201 D1, mus302 D1, mus306 D1 and mus308 D2 ) or repair proficient females. The surviving fraction (dominant lethality) was estimated in the F 1 and used to reassess existing recessive lethal and translocation data. The surviving fraction was found to decrease if repair deficient females were used (maternal effect). The dose-effect curves are often biphasic with a steeper slope at low doses than at high ( ≧5 Gy ) doses of X-rays. The high dose part of the curve is sensitive to oxygenation during irradiation and is affected significantly by the mutants with low fertility ( mei-9, mus101 and mus302). The low dose component is not sensitive to oxygenation during irradiation and seems influenced by all seven repair deficient mutants. The sensitivity of the high dose part to oxygenation suggests that this part is related mainly to DNA break damage, while in the low dose part base damage seems more important. Existing recessive lethal and translocation data were plotted against the surviving fraction for a reassessment. In excision repair deficient mutants translocation induction is lower compared to repair proficient flies at the same level of survival (i.e., dominant lethality). Likewise in post-replication repair deficient mutants induction of recessive lethals is decreased. However the frequency of respectively induced recessive lethals and translocations obtained at the same level of X-rays was the same in repair deficient and proficient backgrounds. It is concluded that genetic damage recovered in a repair deficient background is likely to be qualitatively different even if the frequency of the damage induced by a given dose is not altered.

Evaluation in Drosophila melanogaster of the mutagenic potential of furfural in the mei-9 a test for chromosome loss in germ-line cells and the wing spot test for mutational activity in somatic cells

The mutagenic potential of furfural was evaluated by means of the chromosome loss test in germ cells and the wing spot test in somatic cells of Drosophila melanogaster. The chromosome loss test was carried out employing repair-proficient as well as repair-deficient females. Males carried the compound Y chromosome, B SY y +. Two routes of administration were used: injection and feeding of adult males. Genetic damage was demonstrable after matings of treated males with females carrying the excision repair-deficient mutant mei-9 a. The somatic mutation and recombination test was carried out treating 72-h transheterozygous mwh +/+ flr 3 larvae. Acute treatment of larvae was chosen as the method of exposure. Evidence indicates that furfural induces somatic damage as measured in the wing spot test.

Studies on mutagen-sensitive strains of Drosophila melanogaster: IX. Modification of genetic damage induced by X-irradiation of spermatozoa in N 2, air or O 2 by 4 autosomal repair-deficient mutants

The influence of defects in DNA repair on the recovery of X-ray-induced genetic damage in spermatozoa of Drosophila melanogaster was studied. Basc males were irradiated in N 2, air or O 2 and mated to females of 4 repair-deficient mutant types: mus(2)201 D1 (excision repair deficient), mus(3)306 D1 (excision repair deficient), mus(3)302 D1 and mus(3)308 D2 (both excision repair and post-replication repair deficient). The frequencies of sex-lined recessive lethals and of autosomal translocations in the F 1 progeny were determined following standard genetic procedures. The responses in the different crosses with repair-deficient females were compared to those with repair-proficient mei + females (maternal effects). The main findings are the following: (1) with excision repair-deficient females the frequencies of spontaneous recessive lethals tend to be higher than with mei + females; (2) with excision repair-deficient females the frequencies of recessive lethals induced in N 2 and air and often in O 2 are higher than with mei + females; (3) with post-replication repair-deficient mutants a maternal effect is found for X-ray-induced translocations - both increases and decreases occur depending on the specific mutant type. The data are explained as follows: excision repair deficiencies cause the processing of primary lesions to be diverted from the error-free excision repair to the error-prone post-replication repair pathways. This results in enhanced mutational yields. After irradiation in O 2 secondary effects cause selective elimination of potential recessive lethals in those mutants that exhibit lowered fertility ( mei-9, mus-302). Therefore those mutants have no differential maternal effect on the recovery of recessive lethals after irradiation in O 2. The changes in translocation yield with post-replication repair deficiencies are thought to be the result of defects in the repair of DNA breaks. These defects might cause the post-replication repair deficiency too. The group of post-replication repair mutants is heterogenous. The mutants with low fertility seem to cause decreased translocation frequencies by selective elimination through dominant lethality. The other mutants increase the frequencies.

Studies on mutagen-sensitive strains of Drosophila melanogaster: IV. Modificaiton of genetic damage induced by X-irradiation of spermatozoa and spermatids in N 2 or O 2 by mei-9a, mei-41 D5 and mus(1)101D1

The influence of defects in DNA repair processes on X-ray-induced genetic damage in post-meiotic male germ cell stages of Drosophila melanogaster was studied using the ‘maternal effects approach’. Basc males were irradiated in N 2, air or O 2 either as 48-h-old pupae (to sample spermatids) or as 3–4-day-old adults (to sample mature spermatozoa) and mated to females of 3 repair-deficient strains ( mei-9 a: excision-repair-deficient; mei-41 D5 : post-replication-repair-deficient; mus(1)101 D1: post-replication-repair-deficient and impaired in DNA synthesis). Simultaneous controls involving mating of males to repair-proficient females ( mei +) were run. The frequencies of sex-linked recessive lethals and of autosomal translocations were determined following standard genetic procedures. The responses elicited in the different crosses with repair-deficient females were compared with those in mei + crosses. The main findings are the following: (1) with mei-9 females, the frequencies of recessive lethals are higher after irradiation of spermatids in N 2, but not after irradiation in air of O 2 (relative to those in the mei + crosses); this result is different from that obtained in earlier work with spermatozoa, in which cell stage, higher yields of recessive lethals were obtained after irradiation of males in either N 2 or air; (ii) in the mei-9 crosses, there are no significant differences in response (relative to mei +) after irradiation of either spermatozoa or spermatids in O 2; (iii) the translocation frequencies in the mei-9 crosses are similar to those in the mei + crosses, irrespective of the treated germ cell stage or the irradiation atmosphere; (iv) irradiation of either spermatozoa or spermatids in N 2, air or O 2 does not result in any differential recovery of recessive lethals in the mei-41 relative to mei + crosses; (v) irradiation of spermatids in N 2 and of spermatozoa in air leads to a higher recovery of translocations in the mei-41 crosses; and (vi) after irradiation of spermatids or spermatozoa in any of the gaseous atmospheres, the frequencies of recessive lethals and of translocations are lower in the mus-101 crosses. The differences in responses (between cell stages, in different gaseous atmospheres and with different repair-deficient females) are explained on the basis of both qualitative and quantitative differences in the composition of the initial lesions and the extent to which their repair may be affected by the defects present in the different repair-deficient females. Several discrepancies between expectations based on biochemical results and the genetic results are pointed out. Thus it is made clear that not all the genetic results can be easily explained on the basis of the available biochemical information. On the basis of these and other data from experiments on maternal effects with the repair-deficient mutants, a scheme is presented. This scheme envisages the existence of at least 6 classes of qualitatively different types of initial lesions and of at least as many repair pathways through which these lesions are processed.

Selective elimination of potential ring-X as opposed to rod-X in matings of males treated with diepoxybutane (DEB) to repair-deficient st mus302 females of Drosophila melanogaster.

Evidence is presented demonstrating that diepoxybutane (DEB)-induced ring-X loss in sperm/late spermatids of the Drosophila melanogaster male is substantially lower in matings of ring-X males with repair-deficient st mus302 than ordinary females, but the reverse is obtained when rod-X males are so tested. Taken in conjunction with a higher rate of induced (partial) loss of the rod-Y chromosome of the male with the repair-deficient females suggests the possibility of a greater likelihood that DEB-induced prebreak lesions in ring chromosomes as opposed to rod chromosomes will be eliminated (presumably as a dominant lethals) in the presence of the maternal st mus302 genotype.

Induced chromosom loss following treatment of postmeiotic cells of the Drosophila melanogaster male with MMS and DMN and matings with repair-proficient females and the repair-deficient females mei-9a and st mus302

Drosophila melanogaster ring-X males carrying a double marked Y chromosome, B sY y +, were treated with MMS or DMN and mated with repair-proficient females or the repair-deficient females mei-9 a and st. mus302. Frequencies of induced complete loss (principally the ring-X) and partial losses of the Y chromosome (loss of B s or y +) decreased in the sequence st mus302> mei-9 1>repair-proficient females agreeing with the sequence obtained previously with procarbazine and DEN. With MMS and DMN, some 30–40% or more of partial Y chromosome losses are mosaics from mei-9 a and only 0–4% from st mus302 females suggesting rapid finalization of breaks/pre-break lesions in st mus302 females and a delay in mei-9 a females. Similar findings with procarbazine and DEN are indicated. That the higher sensitivity of st mus302 relative to mei-9 a results from impairments in both postreplication and excision repair in the former remains to be determined.