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T M Yau

Publications and source records attributed to T M Yau.

54 records · Page 3Linked to original sources

Mutagenicity and cytotoxicity of malonaldehyde in mammalian cells.

Malonaldehyde (MA), a lipid peroxidation product derived from polyunsaturated fatty acids, is cytotoxic to a murine L5178Y lymphoma cell line cultured in vitro. Exposure of cells for 24 hours to as little as 20 microM MA produced detectable cytotoxicity as well as an increased number of mutants among survivors, using thymidine or methotrexate resistance as genetic markers. The induced mutation frequency, within the range of MA concentrations tested (10-100 microM), is dose-dependent. Significant division delay, which results in unbalanced growth, is also observed in MA-treated cells. It is suggested that MA crosslinks with DNA and mutagenizes cells through the error-prone repair system. In order to relate the degree of mutagenicity of MA in reference to other mutagenic agents in mammalian cells, the mutation frequency of the thymidine-resistance marker in L5178Y induced by X-irradiation is also presented. The significance of lipid peroxidation in relation to carcinogenesis and the various theories of aging will be briefly discussed.

Animals↗

Effect of low dose rate radiation on cell growth kinetics.

Experimental determinations were made of cell number as a function of time for two strains of L5178Y mammalian cells maintained continuously in various environments of radiation. One strain possessed a shoulder in its dose response curve whereas the other did not. Neither strain showed any significant difference in growth rate for interdivision doses on the order of the median lethal dose or less delivered continuously at a low dose rate or pulsed every 4 h at a high instantaneous dose rate. It was also shown that large numbers of dead cells have little effect on growth rate and that these dead cells last as discrete entities for many days. A simple theory of growth rate in the presence of radiation is presented, and the agreement with the observations implies that there is no effect of any sublethal low dose rate radiation received in one generation on the growth rate or radiation sensitivity of the succeeding generation. Further analysis of the data also showed that for the no-shoulder cells at 37 degrees C, tritiated water had a relative biological effect close to unity for cell sterilization.

Animals↗

Membrane lipid acyl group alterations in cells infected with a temperature-conditional mutant of Rous sarcoma virus.

The increased percentage of oleic acid and decreased percentage of arachidonic acid which occurs in the lipids of chicken embryo fibroblasts transformed by Rous sarcoma virus was shown to be transformation specific rather than a consequence of virus infection. Cells infected with a temperature conditional mutant of Rous sarcoma virus (RSV-T5) had a normal type fatty acid composition when held at the restrictive temperature of 41 degrees C, but had a transformed type fatty acid composition when held at the permissive temperature of 36 degrees C. However, these acyl group changes occurred slowly in the course of transformation, suggesting that they are not a primary event in the genesis of the transformed phenotype.

Animals↗

Alterations in lipid acyl group composition and membrane structure in cells transformed by Rous sarcoma virus.

The acyl group composition of the phospholipids from normal chick embryo fibroblasts and from cells transformed by Rous sarcoma virus was determined by gas-liquid chromatography. Rous-transformed cells had less arachidonate (20:4) and more oleate (18:1) in membrane lipids than normal, growing cells. Normal density-inhibited cells had the lowest ratio of 18:1/20:4. Associated with the decreased content of 20:4 in the transformed cells was a decreased motional freedom of an incorporated spin-labeled fatty acid analogue. Arrhenius plots for uptake of 2-deoxyglucose revealed an increased apparent activation energy in the transformed cells, suggesting that the hexose transport carriers were sensitive to the changes in membrane composition and structure in fully transformed cells. However, the development of the changes in fatty acid composition occurred relatively slowly in the course of transformation, indicating that the observed compositional alterations are not likely to be a primary cause of the early changes in membrane function associated with malignant transformation.

Animals↗

Transport changes associated with growth control and malignant transformation.

We can distinguish two classes of membrane transport changes in cultured cells: (a) growth-rate contingent changes are those which occur in coordination with the onset of density-dependent inhibition of growth; (b) transformation-specific changes are those which occur when cells become transformed, and which can be detected even when normal and transformed cells are growing at the same rate. Growth-rate contingent changes include the density-dependent changes in phosphate, nucleoside, glucose, amino acid, and potassium transport. Only one transformation-specific transport change has been found in Rous-transformed chicken embryo fibroblasts: an increased rate of hexose transport. The variation in potassium transport are associated with variations in the number of ouabain binding sites in the membrane. The molecular basis for changes in the rate of hexose transport is unknown, although gross changes in membrane bilayer composition and "fluidity" seem not to be involved. In analyzing the regulation of hexose transport activity, we find that decreased cAMP may play a role in the transformation-specific increase in hexose transport, but that fibrinolytic activity is not necessary.

Aminobutyrates↗