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Biomedical subjects

R E Meyn

Publications and source records attributed to R E Meyn.

126 records · Page 7Linked to original sources
PubMed1977

Effects of mercuric chloride on synchronized Chinese hamster ovary cells: survival and DNA replication.

Chinese hamster ovary (CHO) cells in vitro were treated with HgCl2 at various stages in the cell cycle and the effects of this chemical on cell survival, DNA replication, and cell division were observed. In terms of survival the early G1 cells were the most sensitive to treatment, followed by late G1 and early S, while mid S and late S-G2 treated cells were the least sensitive. Treatment with HgCl2 also resulted in reduced rates of DNA replication and delays in cell division. The early G1 treated cells showed substantially reduced rates of DNA replication followed by 4--5 h division delay. The early S and late S-G2 treated cells had some reduction in their rates of DNA replication followed by corresponding division delay of 2.5 h in the early S treated cells and 1 h in the late S-G2 treated cells.

Animals↗
PubMed1977

Separation of cells from mouse solid tumors by centrifugal elutriation.

Centrifugal elutriation was used to separate cells dissociated from two hypotetraploid mouse solid tumors, a fibrosarcoma and a sarcoma derived from L-P59 cells, based on their sedimentation rates. The separation was rapid, requiring less than 1 hr; yielded about 80 percent cell recovery; and resulted in little loss of cell viability. Aanlysis of DNA content by flow cytometry demonstrated the synchrony obtained with these tumor cells. The fractions with the lowest sedimentation rates contained predominantly normal cells, those with intermediate sedimentation rates contained predominantly tumor cells in the G1 phase of the cell cycle, and those with the highest sedimentation rates contained mostly tumor cells in S or G2. The clonogenicity of L-P59 cells, assayed in culture, markedly increased with increasing sedimentation rates. In contrast, the clonogencity of fibrosarcoma cells, assayed in vivo by a lung colony assay, was lower for the smaller cells, but was essentially constant among the larger cells. Autoradiography of cells labeled in vivo with tritiated thymidine demonstrated no differences in the proportions of cycling cells in various fractions. These results demonstrate that subpopulations differing in cell type, phase of the cell cycle, and clonogencity can be rapidly separated from solid tumors by centrifugal elutriation.

Animals↗
PubMed1976

Non-histone protein synthesis during G1 phase and its relation to DNA replication.

The kinetics of non-histone chromosomal protein (NHCP) synthesis were studied in Chinese hamster ovary (CHO) plateau phase cells stimulated to proliferate and were compared to NHCP synthesis kinetics in two populations of synchronous G1 traversing cells. In all cases, NHCP synthesis rates increase 3- to 5-fold as cells traversed G1 and attained maximum values one hour before semi-conservative DNA replication began. Similar to results in synchronous G1 cells, the molecular weight distributions of the NHCP fraction from stimulated plateau phase cells underwent only minor changes, measured by sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis, as these cells moved toward S phase. Yet, during this progression after plateau phase and in the transition from early G1 to late G1 in synchronous cells, the total NHCP fraction increased significantly (1.5-2-fold) in amount per cell. These data indicate that plateau phase cells are similar to early G1 cells both in terms of their amounts of non-histone per cell and in their subsequent NHCP synthesis kinetics as they move toward S phase. These results extend previous findings which suggested that NHCP synthesis was coupled to DNA replication and demonstrate that the increased NHCP synthesis and accumulation in chromatin may be a biochemical marker for G1 progression.

Cell Division↗
PubMed1976

Effects of ultraviolet irradiation on the rate and sequence of DNA replication in synchronized Chinese hamster cells.

The effects of ultraviolet light (UV) irradiation on the rate of DNA replication in synchronized Chinese hamster ovary (CHO) cells were investigated. A technique for measuring semiconservative DNA replication was employed that involved growing the cells in medium containing 5-bromodeoxyuridine and subsequently determining the amount of DNA that acquired hybrid buoyant density in CsCl density gradients. One of the advantages of this technique was that it allowed a characterization of the extent of DNA replication as well as rate after irradiation. It was found that while there was a dose-dependent reduction in the rate of DNA replication following UV-irradiation, doses of up to 10 J/m2 (which produce many dimers per replication) did not prevent the ultimate replication of the entire genome. Hence, we conclude that dimers cannot be absolute blocks to DNA replication. In order to account for the total genome replication observed, a mechanism must exist that allows genome replication between dimers. The degree of reduction in the rate of replication by UV was the same whether the cells were irradiated at the G1-S boundary or 1 h into S-phase. Previous work had shown that cells in early S-phase are considerably more sensitive to UV than cells at the G1-S boundary. Experiments specifically designed to test for reiterative replication showed that UV does not induce a second round of DNA replication within the same S-phase.

Base Sequence↗
PubMed1975

Concerning pyrimidine dimers as "blocks" to DNA replication in bacteria and mammalian cells.

Irradiated UV-sensitive bacteria which are mutant in the uvrA6 locus, and cannot excise pyrimidine dimers, are capable of continued DNA replication with the same orientation as that in unirradiated cells. Replication of dimer-containing DNA is also accomplished by irradiated mammalian cells, suggesting that pyrimidine dimers do not act as absolute blocks to DNA synthesis. Thus, the role that dimers play in reducing the amount and size of DNA synthesized after exposure must be reassessed.

Binding Sites↗
PubMed1971

Deoxyribonucleic acid synthesis in ultraviolet-light-irradiated Chinese hamster cells.

Two mammalian cell lines, Chinese hamster ovary (CHO) which can recover colony-forming ability between fractionated doses of ultraviolet light (UV), and Chinese hamster B-14FAF28 which cannot recover, were tested for the ability to bypass UV-induced photoproducts in DNA during postirradiation DNA synthesis. The molecular weight distributions of newly synthesized DNA in UV-irradiated populations of both cell lines showed evidence for photoproduct bypass. Hence, the bypass mechanism does not correlate with recovery after UV.

Animals↗
PubMedDate not supplied

Restoration of bax in prostate cancer suppresses tumor growth and augments therapeutic cell death induction.

BACKGROUND: Cancer cells are characterized by multiple genetic defects which result in altered rates of cell division, cell death and ability to differentiate. These same molecular alterations may also contribute to therapeutic resistance. We examined the potential contribution of the pro-apoptotic gene, bax, to suppressing the growth of prostate cancer cells. MATERIALS AND METHODS: The bax-deficient DU145 prostate cancer cell line was transfected with a hemagluttinin-tagged bax (HA-bax) vector to generate stable expressing bax clones. RESULTS: Ha-bax clones exhibited a significant reduction in tumor growth compared to vector control and parental cells when xenografted into nude mice. HA-bax clones were significantly more sensitive to cell death induction by cis-diamminedichloroplatinum, etoposide, doxorubicin and gamma-radiation than vector control cells. Sensitivity to paclitaxel remained unaltered in the Ha-bax cells. CONCLUSION: These findings suggest that bax may possess a tumor suppressor function in prostatic glandular epithelial cells and be an important determinant of sensitivity to therapeutic cell death induction.

Animals↗
PubMedDate not supplied

Relation of apoptosis to cancer therapy.

Apoptosis, or programmed cell death, is a mode of cell death characterized by distinctive biochemical and morphological features that include endonuclease activation, chromatin condensation and margination, and cellular shrinkage and fragmentation. Its role is homeostatic regulation essential in the maintenance of renewable tissues; the process is controlled by the interaction of genes and tissue-specific hormones or growth factors. A number of apoptosis-regulating genes have recently been discovered including bc1-2, c-myc, and p53. Recent experimental evidence suggests that apoptosis plays an important role in regulation of tumor growth and tumor response to various forms of cancer therapy, including radiotherapy and chemotherapy. Apoptosis develops rapidly, within hours, after cytotoxic treatments and is dose dependent. The apoptotic response correlates well with the antitumor efficacy of radiation and chemotherapy, which makes it a candidate predictor of tumor treatment response. Tumors vary in their apoptotic response to cytotoxic agents, with carcinomas being more responsive than sarcomas. In addition to this intertumor heterogeneity, there is also significant intratumor heterogeneity in apoptosis induction, consistent with the idea that the propensity for apoptosis is genetically regulated. Regulating apoptosis might be an effective way to improve tumor therapy; therapeutic gain would be achieved by increasing apoptotic response of tumors or by inhibiting apoptotic response of normal tissues.

Animals↗