Biomedical subjects
Publications and source records attributed to H Traut.
The induction of 2-break chromosome aberrations (dicentrics and ring chromosomes) in human lymphocytes by the antitumor agents bleomycin and peplomycin is strongly enhanced when those agents are applied together with the heart drug verapamil (isoptin).
The induction of aneuploidy (numerical chromosome aberrations) in oocytes of Drosophila melanogaster by the antitumor drug bleomycin (BLM) was studied with the "aneuploidy pattern method." The aneuploidy pattern obtained after feeding BLM at a concentration of 50 micrograms/ml to Drosophila females resembles the pattern obtained after X-irradiation (3,000 R). This emphasizes the radiomimetic nature of BLM. In addition, new control material is presented. The new control pattern agrees well with that obtained earlier.
Both with a conventional method and with the "aneuploidy pattern method" we tested whether the solvent dimethylsulfoxide (DMSO) is able to induce aneuploidy (numerical chromosome aberrations) in oocytes of Drosophila melanogaster. DMSO was fed as a 2% solution to Drosophila females. No evidence for a mutagenic activity was obtained. This finding and the negative results reported by other authors for other types of mutation in Drosophila show that DMSO can be used as a solvent for chemical agents in mutagenicity screening in Drosophila melanogaster.
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By using an appropriate scheme, various combinations of losses and gains of chromosomes I and II arising in oocytes of Drosophila melanogaster were obtained. The frequencies of these combinations can be arranged as special sequences or patterns which we call "aneuploidy patterns." Aneuploidy patterns were established for spontaneous, colchicine-induced, and X-ray-induced exceptions and were shown to be highly specific for the agent tested. Such patterns can be obtained very quickly, because only exceptional progeny survive. By establishing aneuploidy patterns for chemical agents one would get information of the "aneuploidizing" action of the compounds tested.
The yield of chromosome aberrations (dicentric chromosomes, ring chromosomes) induced in lymphocytes of four radiotherapy patients was determined. In each case this yield was drastically increased when compared with the spontaneous incidence, the dicentric frequencies increasing by the following factors: 604, 525, 600, and 725. With the aid of the dicentric yield obtained, the following equivalent whole body doses were estimated ("biological dosimetry"): 309, 286, 308, and 341 rd. Comparing the observed with the theoretical number of cells with 0, 1, 2, 3 ... dicentrics ("distribution analysis"), we found a highly significant departure from the Poisson distribution, as was to be expected after partial body irradiation. The distribution analysis seems principally suited to discriminate between partial and whole body irradiation.
Although bleomycin (BLM) induces structural chromosome damage, eg, in human lymphocytes, no, or at best a weak, mutagenicity of this substance has been observed after the application of two well-established mutagenicity screening procedures, the Ames test and the sister-chromatid exchange (SCE) test. After feeding BLM to Drosophila melanogaster males we too, observed only a weak mutagenicity as measured by the frequency of recessive sex-linked lethal mutations. These results are based on the analysis of postmeiotic germ cell stages (spermatozoa, spermatids). No autosomal translocations were found in the same experiments. BLM was also fed to Drosophila females under conditions similar or identical to those of the experiments with males. We observed a considerable sensitivity of Drosophila oocytes to the induction by BLM of recessive sex-linked lethal mutations and X-chromosomal aneuploidy (nondisjunction and chromosome loss). Our oocyte results demonstrate that the extensively used antitumor agent bleomycin has to be considered as mutagenic.
In Drosophila melanogaster suppression of oviposition results in an aging of both mature and immature oocytes. When oviposition was suppressed for four days, the incidence of X-chromosomal nondisjunction (XXY exceptions) in mature oocytes was more than doubled, whereas in immature oocytes the nondisjunction frequency was not increased. It is shown that this special susceptibility of mature oocytes to aging-induced nondisjunction has to be considered in experiments on the induction of nondisjunction by chemical agents.
When females of Drosophila melanogaster are treated with chemical or physical mutagens, not only in one but also in both of the two homologous X chromosomes of a given oocyte, a recessive sex-linked lethal mutation may be induced. A method is described that discriminates between such "single" and "double mutations". A theory is developed to show how a comparison between the expected and the observed frequency of double mutations yields an indication of the intercellular distribution (random or nonrandom) of recessive lethal mutations induced by mutagenic agents in oocytes and, consequently, of the distribution (homogeneous or nonhomogeneous) of those agents.--Three agents were tested: FUdR (12.5, 50.5 and 81.0 micrograms/ml), mitomycin C (130.0 micrograms/ml) and X rays (2000 R, 150 kV). After FUdR feeding, no increase in the mutation frequency usually observed in D. melanogaster without mutagenic treatment was obtained (u = 0.13%, namely three single mutations among 2332 chromosomes tested). After mitomycin C feeding, 104 single and three double mutations were obtained. All of the 50 mutations observed after X irradiation were single mutations. The results obtained in the mitomycin C and radiation experiments favor the assumption of a random intercellular distribution of recessive lethal mutations induced by these two agents in oocytes of D. melanogaster. Reasons are discussed why for other types of mutagenic agents nonrandom distributions may be observed with our technique.
Plasma lipid analysis, particularly in population screening, can be facilitated by the use of capillary blood. A system for serial collection of capillary plasma is described. The concentrations of total cholesterol, HDL-cholesterol and triglycerides in heparinized capillary plasma and venous blood, respectively, are compared. No significant differences were found. Using the KAPA-method hemolytic samples are a source of error. They occurred with a frequency of about 3% in mass screening.
18 pregnancies occurred after treatment with bromoergocryptine in 17 patients who wished to conceive, but who suffered from anovulation of varying aetiology. The course of 15 pregnancies was uneventful. Three pregnancies ended in abortion. Nine of the 17 women had hyperprolactinemic amenorrhea. Furthermore, one woman had normoprolactinemic post-pill amenorrhea, another normoprolactinemic anovulatory oligomenorrhea and a third normoprolactinemic anovulatory regular menstruations. With the exception of one woman, all had galactorrhea. The courses of pregnancy were monitored by frequent ultrasound measurements of the fetal biparietal diameter, maternal urinary estriol excretion and radioimmunological measurements of plasma estrone, estradiol, unconjugated and immunoreactive estriol, progesterone, and HPL. All data were within the normal ranges and all babies were healthy at birth and had no teratogenic defects. The data prove the great value of bromoergocryptine in the treatment of hyperprolactinemic anovulation, sometimes even in the treatment of normoprolactinemic anovulation. Moreover, the results indicate no adverse effect on either the course or the outcome of pregnancy.
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After feeding FUdR (5-fluorodeoxyuridine) to female Drosophila melanogaster, highly significant increases in the frequencies of both XO and XXY exceptions were observed in their offspring. The XXY exceptions and part of the XO exceptions result from maternal nondisjunction of the X-chromosomes. Part of the XO exceptions can be assumed to be produced by X-chromosome breakage followed by bridge formation. The analysis of the brood pattern observed suggests that interphase cells (premeiotic oocytes, oogonia) are especially sensitive in the induction of both XO and XXY exceptions by FUdR. In addition, and contrary to the results obtained with other objects, FUdR seems to induce chromosomal damage (presumably chromatid and/or isochromatid breaks) not only in interphase but also in prophase cells. The mechanisms of the induction of X-chromosomal aneuploids by FUdR are discussed.
The fruit fly Drosophila melanogaster is one of the standard systems used for mutagen screening. The colchicine-containing drugs Colchicum-Dispert and Colchysat Burger were fed at extremely low concentrations (1:300 000 and 1:50 000 respectively) to Drosophila females. Among their offspring a remarkably high frequency of aneuploid individuals (XO and XXY flies) were found. These aneuploids correspond karyotypically to the human Ullrich-Turner (XO) and Klinefelter's (XXY) syndromes and result from chromosome loss (XO) and chromosome gain (XXY). The maximum aneuploidy frequency observed after colchicine feeding was 24 times the control value. Depending on their size the aneuploidy frequencies are as great as those obtained by X-irradiation with some hundred or some thousand R.
In a random sample of so-called healthy blood donors under and over 60 years of age (n=196 of 10,593 donations by about 4254 donors) the frequency of antibodies (antibodies against smooth muscles, mitochondria, microsomes, brush border of proximal rat renal tubuli, connective tissue, and parietal cells) detectable by immuno-fluorescence was determined and compared with the incidence thereof in various groups of diseases. In general, two frequency peaks (up to 30 and over 50 years of age) were observed; however, statistical evidence was obtained for the second peak only (with p less than 0.001). In "healthy" blood donors past 60 there was observed a significantly higher frequency of occurrence of antibodies against parietal cells (p less than 0.001) and against connective tissue (p less than 0.01). An attempt has been made to classify antibodies into four groups depending upon age disease, with due consideration being given to the different clinical valency of antibodies. Different frequencies of occurrence of numerous antibodies are believed to be due not only to immune system aging, but especially to the not-yet elucidated disturbance of regulation of autotolerance by alteration of immune cells, which is subject to endogenous (e.g., genetic) and exogenous (e.g. viral) factors that are dependent on age rather than aging.
Anaphase chromosomes exhibit two longitudinal structures which are connected at their ends in a U-shaped closed configuration. The U-shaped ends might be part of the chromosome characterized by a relatively dense condensation of chromosomal material or part of the loop-like structure of the chromosome per se.