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I D Adler

Publications and source records attributed to I D Adler.

At least 109 records · Page 6Linked to original sources
PubMed1982

Germ-cell sensitivity in mammals.

The differences in mammalian germ-cell sensitivity have been studied with a number of mutagenic agents using both chromosomal aberrations and point mutations as genetic endpoints. I have tried to give a survey on the present knowledge. Several conclusions can be drawn at present: 1. In spermatogenesis the sensitivity to mutation induction differs between various post-spermatogonial stages and spermatogonia. 2. Heritable structural chromosomal changes are primarily recovered from post-spermatogonial germ cells. The sensitivity pattern is similar in dominant lethal and heritable translocation experiments. The effect recovered from spermatogonia is near zero. 3. Structurally related chemicals show a difference in their spermatogenic response. The most obvious example gave the induction of specific locus mutations by ENU and MNU. 4. Since too little information is available it seems prudent to assume that oocytes and spermatogonia may show similar sensitivity so that in risk estimates effects on female germ cells cannot be neglected. The final result from the previous discussion must be that the limitations of knowledge are obvious, they lie in the limited number of chemicals tested in mammalian germ-cell assays. A larger data base of mammalian germ-cell response to chemical mutagens is urgently needed.

Animals↗
PubMed1981

Micronucleus test and bone-marrow chromosome analysis: a comparison of 2 methods in vivo for evaluating chemically induced chromosomal alterations.

The sensitivities of 2 cytogenetic tests, chromosome analysis and the micronucleus test, were compared by using mice exposed to the substances methyl methanesulfonate (MMS), mitomycin C (MC) and procarbazine (Natulan). The lowest dose at which a significant effect could be observed in bone-marrow cells of mice was determined. Both test systems proved equally sensitive for MC and procarbazine. Doses as low as 0.16 mg of MC per kg and 3.12 mg of Natulan per kg significantly increased both the aberration rates and the micronucleus rates above those of the controls. In contrast, after exposure to MMS, chromosomal aberrations were elevated above control levels at 5 mg/kg, and the micronucleus rate differed significantly from that of the controls after a dose of 10 mg/kg. With the present protocol and sample size one can conclude that the micronucleus test is generally comparable in sensitivity to the chromosome analysis. However, the MMS data indicate that there might be chemicals for which the resolution of the chromosome analysis is higher. When the mutagens were given in 2 single i.p. injections separated by 24 h, the polychromatic erythrocytes were analyzed for the presence of micronuclei 6 or 24 h after the second injection. The double treatment did not increase the micronucleus rates above the single-treatment results at either sampling interval.

Animals↗
PubMed1980

New approaches to mutagenicity studies in animals for carcinogenic and mutagenic agents. I. Modification of the heritable translocation test.

Two alternative modifications of the experimental protocol for the heritable translocation test are described. One of them proposes to mate F1 males and F1 females within one experimental group and eliminate normal pairs by a sequential decision procedure based on litter sizes. Pairs that do not meet the criteria for normal litter size have to be separated and tested against normal partners. Male translocation suspects are analyzed cytogenetically for presence of a reciprocal translocation. Female translocation suspects or XO suspects are verified through analysis of their male and female progeny. The second modification of the heritable translocation test omits fertility testing and proposes to cytogenetically analyze 25 diakineses-metaphases I from each F1 male in the test. Using either one or both protocols it was shown that 20 mg/kg of methyl methanesulfonate (MMS) induced 1.3% heritable translocations in late spermatids and early spermatozoa. With 2.5 mg/kg of mitomycin C, 0.3% and 0.4% translocation carriers were recovered from treated primary spermatocytes and early spermatids, respectively. A dose of 300 R gamma rays resulted in 1.6% translocations in spermatozoa and 4.8% translocations in primary spermatocytes. The advantage of the modified fertility test lies in the doubling of the sample size by including the females. However, a disadvantage is the amount of time and labor that is necessary to verify female translocation carriers. The cytogenetic translocation test protocol with all F1 males is considered more reliable and faster. It lacks the possibility of error entailed in the decision procedure by fertility testing, and it requires less time, personnel, and animal space.

Animals↗
PubMed1980

A review of the coordinated research effort on the comparison of test systems for the detection of mutagenic effects, sponsored by the E.E.C.

Under the Environmental Research Programme of the Commission of the European Communities a coordinated comparative test programme was started to assess the mutagenic effects of chemicals in as many different assay systems as possible. A preliminary report is given on the results for 5 compounds selected by the Contact Group "Genetic Effects of Chemicals". 11 laboratories contributed data from tests in their expertise. The compounds were methyl methanesulfonate (MMS), N-nitrosodiethylamine (DEN), mitomycin C (MC), procarbazine (Natulan) and atrazine. The results of testing these 5 compounds in more than 20 test systems are still incomplete but some observations can be made at this time. MMS has been shown to be mutagenic in every system used in this collaborative effort which is not surprising in view of the fact that MMS is a widely used reference mutagen that does not require metabolic activation. Among the indirect mutagens which were tested, MC has been shown to be mutagenic with almost every system which has been applied. DEN which requires microsomal activation gave positive results in most submammalian systems as well as in mammalian cells in culture when the S9 fraction of liver homogenate was added. However, in whole mammals most results were negative. One study suggests that the difference in the results with DEN may be due to the short biological half-life of the mutagenically active metabolite. Procarbazine was negative in the microbial tests but gave a positive response in mammalian cells in culture, in Drosophila and in mammals. Atrazine has only been subjected to a limited amount of testing but the results indicate that plant metabolic activation is required in vitro, and that activation to a mutagenic metabolite also occurs in mammals independent from liver enzymes.

Animals↗
PubMed1979

Establishment and characterization of C-type RNA virus-producing cell lines from radiation-induced murine osteosarcomas.

Eight cell lines were established from murine osteosarcomas induced in vivo with the radionuclides 224Ra and 227Th. They have been compared by light and electron microscopy, by karyology, and by their growth properties. The morphology, the growth pattern, and the ability to induce tumors in mice indicate that five of them are tumor cell lines. Chromosome studies demonstrated that the five cell lines have marker chromosomes. The other cell lines only showed some criteria generally used to score for transformation of fibroblasts and they may be derived from stromal cells. All cell lines release virus particles in the culture fluid which have the typical properties of RNA tumor viruses. They possess C-type morphology, a density of 1.16--1.18 g/cm3, a 60--70 S RNA, a RNA dependent DNA polymerase and they induce syncytia in rat XC cells. The possible significance of these virus particles in radiation osteosarcomagenesis is discussed.

Animals↗
PubMed1979

Characterization of feline whole-blood cultures and determination of the frequency of radiation-induced dicentrics in human and feline lymphocytes.

The Ham's F-10 and PHA culture system was applied to whole feline blood and cell-cycle characteristics such as DNA synthesis and mitotic indices were studied. The results are comparable to those obtained from human whole-blood cultures. The yields of dicentrics were also determined in lymphocytes from X-irradiated human and feline blood. The ratio between the experimental yields of dicentrics in human as compared to feline lymphocytes was 1:0.27.

Animals↗
PubMed1978

The effect of isoniazid (INH) on Chinese hamster and mouse spermatogonia.

Acute and chronic treatment of Chinese hamsters and mice with 5, 25 and 125 mg/kg isoniazid (INH) given by oral intubation did not enhance the chromosomal aberration frequencies in spermatogonia. The structural and numerical aberration rates remained in the range of spontaneous events even after the chronic treatment over 12 weeks with 3 x 125 mg/kg INH per week. This dose is much higher than normally used for prevention and therapy in man (3--16 mg/kg).

Animals↗
PubMed1978

Cytogenetic study in spermatocytes of mice and Chinese hamsters after treatment with isoniazid (INH).

Meiotic chromosomes of spermatocytes from INH-treated male mice and Chinese hamsters were analysed for chromosome aberrations in diakinesis-metaphase I and metaphase II. The experiments were performed in two laboratories while a third laboratory participated in the chromosome evaluation. No enhancement of chromosome aberrations could be observed after acute treatment of early primary spermatocytes or chronic treatment of spermatogonia with INH.

Animals↗
PubMed1978

Effects of isoniazid (INH) on the oogenesis of mice.

Mutagenic damages in female germ cells of mice have been tested with the dominant lethal assay and the cytogenetic analysis of unfertilized M II-oocytes. Concluding one can say that from the experimental data presented here do not show any mutagenic effect of INH on oogenesis of different strains of mice can be stated.

Animals↗
PubMed1977

Heritable translocation test and dominant-lethal assay in mice with methyl methanesulfonate.

A dominant-lethal test and a heritable translocation test were performed with methyl methanesulphonate (MMS) at 40 mg/kg by treating the sensitive periods of post-meiotic spermatogenesis i.e. spermatozoa and spermatids. In the dominant-lethal test 25 to 60% dominant-lethal mutations were obtained depending on the mating intervals. In the heritable translocation test 11% sterile and partially sterile F1 males were observed in 250 offspring of the MMS group. All of the 14 partially sterile and 6 of the 14 sterile F1 males were demonstrated to be translocation carriers. Fertility of the partial steriles was about 40% of normal fertility. The translocation frequencies in the primary spermatocytes of the partially sterile F1 males varied between 2 and 99%. Transmission of partial sterility and translocations was confirmed in the F2 generation. There were no partially sterile or sterile males among the 245 controls.

Animals↗
PubMed1977

Stage-sensitivity and dose-response study after gamma-irradiation of mouse primary spermatocytes.

The sensitivity pattern for X-ray-induced chromatid aberrations was analysed in primary spermatocytes irradiated at 1 to 11 days diakinesis-metaphase I of meiosis. Using a dose of 300 R (60 R/min) of gamma-rays zygotene (day 9) was found to be the most sensitive and leptotene (day 11) the most insensitive stage. The dose-response to gamma-ray-induced aberrations was evaluated in cells irradiated zygotene. Both the yields of rearrangement as well as the yields of fragments gave a best fit to a quadratic model.

Animals↗
PubMed1976

Aberration induction by mitomycin C in early primary spermatocytes of mice.

MC is well known to induce dominant lethal mutations in mouse spermatocytes. Tests were done to determine whether chromosomal aberrations could be identified in spermatocytes as being responsible for the dominant lethal effects. Male mice were treated with single doses of MC during DNA synthesis preceding meiosis and during early prophase of meiosis. Simultaneous labeling was performed to identify cells that were in S-phase during the time of treatment. Diakineses-metaphases I were analyzed for the occurrence of univalents, gaps, fragments and rearrangements. The frequencies of cells with aberrations increased with dose and time after treatment. Maximal values were obtained after 12 days, indicating that MC was most effective in cells undergoing DNA replication. 95% of these cells were labeled. The majority of aberrant cells contained one or more fragments. These cells will lead to dominant lethality of the zygotes after fertilization. Cells with rearrangements occurred 11 and 12 days after treatment. These cells can develop into sperm carrying a reciprocal translocation which would then give rise to semi-sterile progeny after fertilization. Further investigations are needed to study the transmission of rearrangements observed in primary spermatocytes.

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