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S Wolff

Publications and source records attributed to S Wolff.

At least 19 recordsLinked to original sources
PubMed1979

The apparent decrease in thiotepa-induced chromosome aberrations in human lymphocytes caused by an effect of WR2721 on the cell cycle as found by the definitively determined division method.

Antimutagenic radioprotective compounds have been reported to decrease the yield of chemically induced chromosome aberrations even when administered long before the chemical mutagen thio-TEPA. Because thio-TEPA can induce aberrations in all parts of the cell cycle, it seemed likely that the apparent decrease in aberrations was the result of an effect of the antimutagen on the progression of cells through the cell cycle so that cells treated in the more sensitive stage would be scored. To test this possibility human lymphocytes were treated with the protective compound WR2721 and then thio-TEPA. The cells were grown in the presence of 5-bromodeoxyuridine, which allows the definitive determination of metaphases from cells that divided once, twice, or three times after treatment. The yield of aberrations observed in first division cells was the same whether or not the protector was present. A decrease in aberration yields appeared only in rapidly cycling cells that were in the second division at the time of fixation. Labeling experiments showed that in this rapidly dividing population fewer of the metaphase cells had been in G2 when thio-TEPA was added. The results indicate that part of the decrease in aberration yields obtained by treatment with an antimutagen several hours before the addition of a mutagen is an artifact of cell selection.

Amifostine↗
PubMed1979

The relation between chemically induced sister-chromatid exchanges and chromatid breakage.

Studies of classical chromosome aberrations and sister-chromatid exchanges (SCES) suggest independent mechanisms for the two events despite some common features. Examination of chromosome breakage caused by X-rays, visible light, and viruses has shown that few chromatid breaks are accompanied by SCEs at the sites of breaks. No similar observations were available for chemically induced breaks, but it has been reported that rat chromosomes exposed to dimethylbenzanthracene (DMBA) contained a preponderance of both aberrations and SCEs in certain specific regions, implicating a common process in their formation. These conclusions were drawn from a comparison of breaks induced in vivo with SCEs induced in vitro. However, we used 7 chemical mutagens to induce both chromatid breaks and SCEs in "harlequin" chromosomes of cultured rat and Chinese hamster ovary (CHO) cells and found that 25% of the 914 breaks scored were associated with SCEs. The proportion of breaks accompanied by SCEs is related to the overall SCE frequency and falls into the range predicted on the basis that breaks and SCEs occur independently. The reported association between sites for SCEs and aberrations also reflects secondary factors, such as induction of SCEs and aberrations during DNA synthesis in late replicating regions of the chromosomes.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Sister chromatid exchanges induced by inhaled anesthetics.

There is sufficient evidence that anesthetics may cause cancer to justify a test of their carcinogenic potential. Baden, et al., using the Ames test, a rapid and inexpensive genetic indicator of carcinogenicity, have shown that among currently used anesthetics fluroxene alone caused bacterial mutations. The authors used the sister chromatid exchange (SCE) technique, another rapid assay of mutagenic-carcinogenic potential. The frequency of sister chromatid exchanges in Chinese hamster ovary cells increases when the cell cultures are exposed to mutagen-carcinogens, particularly in the presence of a metabolic activating system. With this test system a one-hour exposure to 1 MAC nitrous oxide, diethyl ether, trichloroethylene, halothane, enflurane, isoflurane, methoxyflurane, or chloroform did not increase SCE values. Divinyl ether, fluroxene and ethyl vinyl ether increased SCE values in the same circumstances. Results of this study of mammalian cells suggest that no currently used anesthetic is a mutagen-carcinogen. The results also suggest that anesthetics containing a vinyl moiety may be mutagen-carcinogens.

Anesthesia, Inhalation↗
PubMed1978

Chromosomal isolabelling caused by three rounds of synthesis in late replicating regions.

Isolabelling only occurs in CHO cells that have been allowed to replicate for more than 2 but less than 3 cell divisions in the presence of BrdU. The isolabelling is confined to late replicating regions of the chromosomes. The staining patterns obtained indicate that BrdU was incorporated three times in these regions and that the isolabelling did not come from the segregation of label in polynemic chromosomes.

Autoradiography↗
PubMed1978

Saccharin-induced sister chromatid exchanges in Chinese hamster and human cells.

Since the induction of sister chromatid exchanges in cultured cells has been shown to be the most sensitive mammalian system to detect the effects of mutagenic carcinogens, Chinese hamster ovary cells and human lymphocytes were exposed to the sodium saccharin found to induce bladder cancer in rats. Both that saccharin and a highly purified extract of it increased the yield of sister chromatid exchanges in both types of cells. The results, which were repeatable and statistically highly significant, indicated that the weak carcinogen, saccharin, is also mutagenic in the sense that it induces cytogenetic changes.

Cell Line↗
PubMed1978

Sister-chromatid exchanges induced in rabbit lymphocytes by 2-aminofluorene and 2-acetylaminofluorene after in vitro and in vivo metabolic activation.

Because short in vitro treatments of Chinese hamster cells with 2-aminofluorene and 2-acetylaminofluorene did not increase SCEs even in the presence of a metabolic activation system, experiments were carried out with rabbits to see if in vivo activation occurred. Rabbits injected with 2-AF could activate the compound and a transient dose-dependent increase in SCEs was found in peripheral lymphocytes cultured at various times after the injection. With 2-AAF, however, the response was more variable: some rabbits showed an increase immediately, but one showed an increase only after a subsequent injection. This indicated that among rabbits differences exist in their ability to detoxify 2-AAF. Because rabbits could activate the compounds, in vitro experiments were carried out to see if their lymphocytes responded differently from Chinese hamster cells and to see if the metabolic changes brought about by PHA stimulation affect the ability of the cells to activate the chemicals. The addition of PHA and the consequent metabolic stimulation do affect the induction of enzymes involved in the activation of 2-AF and 2-AAF. Benzo[alpha]pyrene, in contrast, can be activated by rabbit lymphocytes independently of PHA stimulation.

2-Acetylaminofluorene↗
PubMed1978

Molecular suicide studies of 125I and 3H disintegration in the DNA of Chinese hamster cells.

The shape of the survival curve for cells inactivated by tritium decay in DNA is modified by the presence of halogenated pyrimidines in the DNA in a manner analogous to their effect on X-ray induced reproductive death. The large shoulder found for tritium suicide is removed completely by coincorporation of 10(-6) M IUdR. The oxygen enhancement ratio for 125I and tritium disintegrations in unsynchronized Chinese hamster cells was determined for cells permitted to accumulate damage from these events at 4 degrees C. The oxygen enhancement ratio for 125I induced damage is 1.4. This is much smaller than the OER found for tritium decay which is similar or more than that found for X-ray exposure under the same conditions. These results suggest that the nature of the lesions produced by 125I decay in DNA are analogous to those produced by high LET radiation while those lesions produced by tritium are similar to lesions produced by roentgen rays. In synchronous V79 cells the effects of 125I induced damage in different regions of the mammalian cell DNA was examined taking advantage of the fact that DNA replication in hamster nuclei follows a time-dependent three dimensional pattern. The experiments indicate that 125I decays accumulated in the G2-period of the cell cycle have different efficiences for the induction of reproductive death depending on the region of the DNA which is labeled. The efficiency for the induction of reproductive death appears to be a maximum in DNA that replicates in V79 cells near the end of the DNA replication cycle. Electron capture events are dramatically efficient in the production of lethal chromosome aberrations. In CHO cells synchronized in the G1-stage of the cell cycle stored in the frozen state the efficiency for the induction of dicentric and ring chromosomes is 0.03. The dose response curve for the induction of these aberrations is linear in contrast to the curvilinear response found for roentgen ray exposure under the same conditions. Data on this kind suggest that there may exist "critical" regions within mammalian cell nuclei where chromatin fibers from two different chromosomes are in close proximity to each other and both are damaged non-repairably by a single electron capture event.

Animals↗