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J W Simons

Publications and source records attributed to J W Simons.

137 records · Page 8Linked to original sources
PubMed1975

A mutational assay system for L5178Y mouse lymphoma cells, using hypoxanthine-guanine-phosphoribosyl-transferase (HGPRT) -deficiency as marker. The occurrence of a long expression time for mutations induced by X-rays and EMS.

The development of a system for the detection of somatic cell mutation to hypoxanthine-guanine-phosphoribosyl-transferase (HGPRT) (EC 2.4.2.8) deficiency in L5178Y mouse lymphoma cells is described. The selection of mutant cells was not influenced by the concentration of the selective agent 6-thioguanine (6-TG). In addition, all the mutants selected, spontaneous as well as induced ones, showed a complete loss of HGPRT activity. In reconstruction experiments, in which mutant cells were mixed with wild-type cells, the recovery of mutant cells was only markedly influenced when wild-type cells were seeded in a cell density ten times higher than the one, 5-10(4) cells/ml, used in subsequent induction experiments. X-irradiation and treatment with ethyl methanesulfonate (EMS) increased in the mutation rate above the spontaneous background. A clear-cut dose-dependent mutagenic effect after exposure to X-rays was measured. The rate of induced mutations at the HGPRT locus in lymphoma cells was 1-3-10(-7) per R, as determined after exposures of 200, 300, 400, 500 and 600 R. The time the cells needed to express their mutations was much longer than 48 h. Further study of this phenomenon showed that the optimal expression time for TGr-resistant mutants in L5178Y cells was 6 to 7 days. No indication for a dose-dependent effect on the optimal expression of the mutants was found.

Animals↗
PubMedDate not supplied

Recovery of growth-arrested human fibroblasts from UV-induced lethal damage is inhibited by low cell density or sodium butyrate.

The influence of growth arrest on recovery from UV-induced lethal damage in human fibroblasts was investigated. Cells were arrested in G1 either by confluent holding (high cell density at 37 degrees C) or by temperature holding (low cell density at 30 degrees C) or by a combination of both methods. These experiments showed that survival recovery only occurred in cells arrested at high cell density, both at 37 degrees C and at 30 degrees C, and not in cells arrested at low cell density at 30 degrees C. Furthermore, it was demonstrated that the rate of transcription in unirradiated cells arrested at high density, both at 37 degrees C and at 30 degrees C, was much lower compared to that in cells arrested at low density. These observations can be explained by assuming that impaired transcription is responsible for UV-induced cytotoxicity and that recovery of RNA synthesis due to repair of damage in transcriptionally active genes may account for survival recovery. Sodium butyrate did not influence the absence of recovery during low temperature holding at low density but inhibited survival recovery during confluent holding. Sodium butyrate might prevent survival recovery at high cell density by inducing a chromatin structure resembling that of untreated cells arrested at low density.

Butyrates↗
PubMedDate not supplied

Differential response of human fibroblasts to the cytotoxic and mutagenic effects of UV radiation in different phases of the cell cycle.

The effects of DNA repair on UV-induced mutagenesis and cell killing in human diploid skin fibroblasts in different phases of the cell cycle were studied. The cells were synchronized in G1 by culturing at 30 degrees C. Using this synchronization method, it could be demonstrated that cells irradiated at 30 degrees C and allowed to carry out excision repair for various lengths of time, show a much lower mutation frequency than cells irradiated in the exponentially growing state. Irradiation in early G1 gives rise to less mutations than irradiation in S. However, the surviving fraction is not decreased when cells are irradiated in S in comparison with irradiation in G1. Moreover, there is no recovery from UV-induced lethal effects when irradiated cells are kept stationary at 30 degrees C for various periods of time. This is in contrast with the results obtained with density-inhibited fibroblasts held at 37 degrees C, which show a recovery from the UV-induced lethal effects.

Cell Cycle↗
PubMedDate not supplied

Genetic, epigenetic, dysgenetic and non-genetic mechanisms in tumorigenesis. II. Further delineation of the rate limiting step.

A not yet understood phenomenon in carcinogenesis is presented by the enormous species-specific and age-specific differences in cellular susceptibility to malignant transformation. Murine cells are 100,000 times fold more susceptible than human cells. A previous review article suggested the promotion phase as the key for this difference. Presently, a further analysis of literature data indicates that promotion results in the dedifferentiation of cells, which, in initiated cells, leads to an imbalanced regenerative growth of stem-cell-like cells. As aging results in the loss of adaptive functions and in a decreased response to growth stimuli, dedifferentiation of old cells is supposed to increase the imbalance of the regenerative growth for initiated cells and consequently to enhance the chance for immortalization of these cells. As immortalization is accompanied by chromosomal dysgenetics, malignant conversion by the appearance of secondary genetic events during multistage carcinogenesis is not just a matter of random chance for additional mutations, but is determined to some degree by the condition of the initiated target cell and to the species to which the target cell belongs.

Aging↗