O. G. Fahmy
Articles written in Journal of Genetics
Volume 52 Issue 3 September 1954 pp 603-619
Dominant lethals induced by 2:4:6-tri(etkyleneimino)-1:3:5-triazine are due to noneucentric chromosome configurations that result in anomalous cleavage and the eventual arrest of embryonic development. The variation in the frequency of these lethals with the dose of the compound (in molar concentration) follows the same pattern as for X-rays. The curve governing this relationship when plotted semi-logarithmically approximates linearity at low doses but proceeds with a sharper gradient as the dose increases. The yield of dominant lethals by the chemical mutagen is consistently higher than mutagenically equivalent doses of X-rays, assessed on the basis of sex-linked recessive lethals.
The quantitative theory of dominant lethals (Haldane & Lea, 1947) deduced on the basis of sister union of single-chromosome breaks and asymmetric rearrangements among two or more, was found to explain the dose/effect relationship for the chemical mutagen. The experimental dose curve was successfully fitted, and it was possible to evaluate the constants describing the properties of the induced chromosome breaks.
The yield of dominant lethals under the effect of the inline studied varies with the stage of spermatogenesis at the time of treatment. The sensitivity pattern for the various cell stages was deduced, whence it was found that the sperm was the most susceptible This constitutes a difference from X-rays, where the most sensitive stage is an earlier germ mother cell.
Volume 53 Issue 1 January 1955 pp 181-199
Chromosome rearrangements induced by various doses of 2:4:6-tri(ethyleneirnino)-l:3:5-triazine in
Volume 53 Issue 3 September 1955 pp 563-584
Cytogenetic analysis of the action of carcinogens and tumour inhibitors in
The mutagenic response of the various stages of spermatogenesis to the action of 2:4:6-tri(ethyleneimino)-l:3:5-triazine has been investigated by the brood technique. The treated male was mated to a succession of virgin females at set intervals, and the mutation rate was scored separately in each brood. The mutation rate/brood relationship for the same genetic property varied in the different experiments. It was found to depend on the structure of the testis at the time of treatment and the gross morphological changes induced in it by the mutagen. Another controlling factor is the way the male germ line is fractionated among the broods, which varies with the rate of germ-cell differentiation and the brood interval. To reduce variability between experiments a standard technique was adopted. The treated males were of the same strain, age and size, were reared under the same culture conditions and their progeny was fractionated at fixed intervals.
Volume 54 Issue 1 January 1956 pp 146-164
Chemical mutagens have been shown to act on gene loci which are apparently stable to X-radiation. By the use of a group of alkylating compounds it was possible to induce nearly 200 ‘new’ sex-linked recessive visibles (ranks 1 and 2), different in phenotype and genetic position from those induced by the physical agent.
The ratio of sex-linked recessive visibles/lethals in the same sample of treated chromosornes is exceptionally high for a particular amino-acid mustard (
The distribution of the loci of recessive lethals along the X-chromosome is the same for three representative alkylating mutagens, and is significantly different from that for X-rays. A significant difference also occurs in the distribution of the
The rate of induction of small deficiencies by the alkylating compounds is nearly twice that produced by mutagenically equivalent doses of X-rays. Evidence is available that chemically induced deficiencies result from errors in gene reproduction rather than chromosome breaks.
There is a shortage in major structural rearrangements in viable sperm, as well as among the sex-linked recessive lethals, under the effect of the alkylating agents compared with mutagenically equivalent doses of X-rays. This shortage, in the case of the tri(ethyleneimino)triazine rearrangement lethals, has been shown to be due to differences in the properties of the chromosome breaks induced by the imine and X-rays, rather than a lower efficiency in the induction of the primary chromosome breaks by the chemical agent.
The dose effects as regards the induction of sex-linked recessive lethals, dominant lethals and viable chromosome breaks, are identical for tri(ethyleneirnmo)triazne and X-rays. This suggests that the hypothesis of direct action of radiations on the genetic material is not conclusively proved by evidence based solely on dose relations.
Among the sex-linked recessive lethals induced by various closes of tri(ethyleneimiao)triazine there is a fixed proportion showing cytoiogically detectable chromosome aberrations: major rearrangements and deficiencies. Within this fixed proportion, the fraction with rearrangements increases and that with deficiencies decreases with increase in dose. The bearing of this observation on the mechanism of induction of chromosome breaks by chemical means has been outlined.
Volume 55 Issue 2 July 1957 pp 280-287
A sample of X-ray sex-linked recessive lethals has been localized by the same marker chromosome, and under identical experimental conditions, as prevailed in the placing of the same mutations induced by the alkylating compounds, so as to insure homogeneity of localization. The distribution of this sample of X-ray lethals along the X-chromosome varied significantly from that for the chemically induced mutations.
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