Section 5 — Mutagenesis 



acute doses of 55r, HOr, 160rand 3 lOr gave a clear- 

 ly non-linear dose-effect curve for sex-linked re- 

 cessive lethals. In order to explain the results, a 

 mathematical model for the irradiated cell pop- 

 ulation has been formulated, considering cell 

 killing, variation in sensitivity to killing and to 

 mutation induction with cell cycle stage, and 

 length of cell cycle. Thus, the frequency of mu- 

 tations observed will be equal to the product of: 

 dose absorbed by sensitive cells number of 

 sensitive cells : sensitivity of sensitive cells 

 survival of sensitive cells, divided by: total 

 number of cells in population less killed sensi- 

 tive cells. In this first approximation, effects on 

 resistant cells have been disregarded. According 

 to this model, protraction of doses in this dose 

 range should lead to higher yields of mutants. 

 Protraction of 144 r, 267 r, and 542 r over 8 hr 

 (four spermatogonia! cell cycles in the irradiated 

 embryo), have given results in support of the 

 hypothetical model, showing a linear increase in 

 mutation rate with dose, with a slope higher than 

 2 10 -5 sex-linked lethals per r, indicating a sen- 

 sitivity at least as high as for mature sperm, for 

 doses lower than a few hundred r. 



The work has been supported by The Nor- 

 wegian Cancer Society. 



5.44. Modification of the X-ray induced Rate of Sex- 

 linked Lethals by Nitrogen Post-treatment and 

 Fractionation of the Dose in Drosophila melano- 

 gaster. A. D. TATES(Leyden, The Netherlands). 



Male flies carrying a ring X-chromosome, were 

 exposed to a flow of purified nitrogen for 25 min, 

 immediately after having received a dose of 

 1450 r (55 r/sec). Results of five independent ex- 

 periments show a significant increase of mutation 

 frequency due to post-treatment in spermatids 

 and late spermatocytes, 9.5 per cent lethals (3744 

 tested chromosomes) were found after irradiation 

 without post-treatment and 10.8 per cent lethals 

 (5190 chromosomes) with N 2 post-treatment; 

 normal deviate = 2.21 and/> = 0.0139. A possible 

 interpretation of the results is that N 2 post- 

 treatment blocks repair of pre-mutational dam- 

 age. 



In two experiments a third group of flies re- 

 ceived N 2 post-treatment after a delay of 25 min. 

 A comparison of the results of delayed versus 

 direct post-treatment shows a significant de- 

 crease of the mutation rate in the group with 

 delayed post-treatment. The percentage for the 

 direct treatment is 9.54 per cent (2222 chrom.) 

 and for the delayed treatment 7.15 per cent (2545 



chrom.); normal deviate 2.538 and P = 0.0055. 

 This result suggests that in young spermatids and 

 late spermatocytes repair, under these experi- 

 mental conditions, is completed within 25 min. 

 Five experiments were carried out to investi- 

 gate whether dose fractionation favours repair. 

 The mutagenic effects of a dose of 1350 r given 

 in five equal fractions, seperated by two hour- 

 intervals, were compared with that of unfractit 

 onated irradiation. The results show a significan- 

 decrease of mutation frequency due to fraction- 

 ation, in the same germ cell stages where N 2 _ 

 post-treatment had been effective. Percentages 

 of lethals for the fractionated and unfractionated 

 groups are 8.63 per cent (4994 chrom.) and 9.77 

 per cent (4676 chrom.) respectively (normal 

 deviate 3.01 and P = 0.0013). 



5.45. Oxygen Effects and Dose Fractionation in the 

 Developing Germ Cells of Drosophila virilis. 



Mary L. Alexander (Austin. U.S.A.). 



One-day-old males of D. virilis were treated 

 with lOOOr of X-rays while under 74.7 lb pressure 

 of argon gas and in a gaseous atmosphere of 

 45 lb argon + 19.7 lb oxygen. X-rays were given 

 at a rate of lOOOr/min as a single dose and as two 

 doses fractionated by a period of 40 min. Ad- 

 ditional tests were made with 2000r under 64.7 lb 

 of argon. Postmeiotic, meiotic and premeiotic 

 germ cells were tested for induced biological 

 damage. 



Dominant lethals in postmeiotic sperm and 

 spermatid cells were increased by the presence of 

 oxygen. In sperm and spermatids, there were no 

 differences in the percentages of dominant lethals 

 or translocations with dose rate changes in argon 

 or when oxygen was present. These results 

 differed from those observed for D. melanogaster 

 where dose fractionation in argon, but not oxy- 

 gen, increased translocations, sexlinked lethals 

 and dominant lethals in spermatids. The pre- 

 meiotic cells of virilis, as melanogaster, showed 

 an enhancement in dominant lethals with dose 

 fractionation in both anoxic and oxygenated 

 gases. Enhancement with dose fractionation in 

 virilis appears to be limited to later sperma- 

 togonia! stages. The stem cells do not respond to 

 dose fractionation. 



Enhancement of lethals in premeiotic cells has 

 been observed in anoxic and oxygenated atmos- 

 pheres of gases in both species. Differences in 

 response of spermatid cells in virilis and melano- 

 gaster may be due to oxygen metabolism or 

 other metabolic differences in the two species. 

 Speimatogenic cysts are not prevalent in young 

 males of either species and the differences cannot 



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