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Biomedical subjects

C C Chang

Publications and source records attributed to C C Chang.

At least 595 records · Page 33Linked to original sources
PubMed1983

Oncogenes, inhibited intercellular communication and tumor promotion.

Homeostatic control of proliferation and differentiation is characteristic of normal, but not malignant, cells. Gap junction-mediated intercellular communication provides one mode of this homeostatic control for cells in physical juxtaposition. Many chemicals, both natural and human-made, can modulate the function of gap-junctional communication and by doing so, alter the control of proliferation and differentiation of cells. Many of these chemicals are known tumor promoters. Oncogenes appear to be highly conserved genes influencing proliferation and differentiation of cells. We have speculated that certain oncogenes might play a role in tumor promotion by their influence on the regulation of gap-junctional intercellular communication. If this hypothesis is correct, a mechanism would exist to unify radiation, chemical and viral carcinogenesis.

Animals↗
PubMed1983

Aphidicolin-induced endoreduplication in Chinese hamster cells.

Aphidicolin, a specific inhibitor of DNA polymerase alpha, was found to induce high frequencies of endoreduplication in Chinese hamster V79 cells in a dose-dependent manner. The aphidicolin-induced endoreduplication was observed when cells were incubated at 37 degrees but not at 41 degrees. Since it is known that DNA polymerase beta is more thermally labile than is DNA polymerase alpha, the data are consistent with the hypothesis that DNA polymerase beta might be responsible for endoreduplication as was reported in mouse trophoblast cells. From the induced diplochromosomes, it was observed that the two unifilarly 5-bromodeoxyuridine-substituted chromatids are generally paired and located inside, whereas the two bifilarly 5-bromodeoxyuridine-substituted chromatids are flanking outside regardless of the presence of sister chromatid exchange or intradiplochromatid interchange.

Animals↗
PubMed1983

Dissociation in expression of MB1/MT1 and DR1 alloantigens in mutants of a lymphoblastoid cell line.

Cytotoxicity tests with alloantisera were used to study the expression of HLA-D region antigens in HLA-DR-null mutants of a human lymphoblastoid cell line. The initial cell line contained just one copy of the MHC as a haplotype that included DR1 and MB1/MT1. Gamma ray mutagenesis of the single haplotype cells followed by selection with complement and an anti-DR monoclonal antibody were then used to isolate DR-null mutants. Two categories of mutants were identified with a panel of alloantisera. Expressions of DR1 and MB1/MT1 were simultaneously lost in four mutants. Nine mutants still expressed MB1/MT1 but had lost the expression of DR1. The dissociated loss of expression of MB1/MT1 and DR1 antigens is evidence for separate genetic control of these alloantigens. The methods used exemplify a versatile approach for conveniently inducing separations of closely linked loci of the MHC.

Cell Line↗
PubMed1982

Revertants of a Chinese hamster ovary cell mutant resistant to suppression by an analogue of cholesterol: isolation and partial biochemical characterization.

A highly efficient selection procedure was developed for isolating revertants of Chinese hamster ovary (CHO) cell mutants resistant to suppression by 25-hydroxy-cholesterol. The procedure is based on the fact that the specific polyene antibiotic amphotericin B caused a lethal porous complex formation with membrane cholesterol only in cholesterol-rich cells. The wild-type cells and the revertant cells switched to grow from fetal calf serum medium to delipidated fetal calf serum medium for approximately 1 day became deficient in cellular cholesterol content. These cells, unlike the cholesterol-rich mutant cells, became much less sensitive to amphotericin B cytotoxicity. The spontaneous reversion frequency of a previously reported 25-hydroxycholesterol-resistant cell clone, 25-RA [Chang, T.-Y., & Limanek, J.S. (1980) J. Biol. Chem. 255, 7787-7795], was found to be approximately 3 X 10(-6), a frequency comparable to other single gene mutations of CHO cells. Biochemical analyses of three of these revertants showed that all defects manifested in 25-RA cells reverted back in parallel, a result suggesting that these observed defects in 25-RA cells are due to a single mutation event, thus supporting the hypothesis (Chang & Limanek, 1980) that a common controlling factor may be involved in mediating the suppressive action(s) of the cholesterol analogue on various cholesterogenic enzyme activities. The function of this common controlling factor is rendered abnormal in 25-RA cells by mutation.

Amphotericin B↗
PubMed1982

Some stereochemical features of aspartate beta-decarboxylase.

Aspartate beta-decarboxylase catalyzes abortive decarboxylation/transamination of [2-3H]aspartate with at least 17% internal transfer of tritium to the pro-S position at C-4' of the resulting pyridoxamine phosphate. In the normal beta-decarboxylation reaction, at least 1.06% of the tritium from the alpha-position of aspartate appears in the product alanine. The enzyme catalyzes slow hydrogen exchange from the beta-position of alanine but not aspartate. The replacement of the beta-carboxyl group of aspartate by hydrogen occurs in an inversion mode. These results are interpreted in terms of a two-base mechanism.

Alcaligenes↗
PubMed1982

The role of inhibited cell-cell communication in teratogenesis.

A mechanistic link between teratogenesis and carcinogenesis has been suggested by a wide variety of scientific observations. This report attempts to provide a theoretical explanation for one of the several possible mechanisms which might be shared during carcinogenesis and teratogenesis. The initiation and promotion concept of carcinogenesis was briefly reviewed and the role of intercellular communication during the complex tumor promotion phase was discussed. Inhibition of intercellular communication by a wide variety of physical, chemical and biological factors was speculated to disrupt the regulation of proliferation and differentiation in stem cells. Chemicals, which interfered with intercellular communication during early organogenesis, have the potential of being teratogens, while if they are present in the developed, initiated organisms have the potential of being tumor promoters. Evidence was presented showing that known tumor promoters which inhibited intercellular communication also had been shown to be teratogens. It was concluded that in vitro assays, designed to measure intercellular communication, although having known limitations, might be used as an in vitro means to screen for potential teratogens.

Abnormalities, Drug-Induced↗
PubMed1982

The varying tissue distribution of L-glutamic acid labelled at three different sites.

Methods using 5 and 6 enzymes were devised to synthesize L-[11C]glutamic acid (GA), labeled on the carboxyl group of either the alpha-(AGA) or gamma-(GGA) carbon atom. The distribution of the 11C-labeled AGA or GGA in rabbits was compared with that of L-[13N]glutamic acid. The results show that AGA was rapidly decarboxylated with loss of the 11C-label, and that GGA was also decarboxylated, but to a lesser degree. Thus, the radiolabel distribution may not reflect the distribution of the original compound. The results also demonstrate that positron labeled pharamaceuticals may be rapidly synthesized via complex enzymatic pathways.

Animals↗
PubMed1982

Association of mutator activity with UV sensitivity in an aphidicolin-resistant mutant of Chinese hamster V79 cells.

The spontaneous mutation rates of an ultraviolet light (UV)-sensitive aphidicolin-resistant mutant (aphr-4-2) and its revertants have been determined by 2 techniques. By using the fluctuation analysis, the mutant and its thymidine (TdR)-prototrophic 'revertant' were found to exhibit elevated spontaneous mutation rates at the 6-thioguanine- and diphtheria-toxin-resistant loci. In contrast, the TdR-auxotrophic 'revertant' did not show this property. Similar results were obtained by the multiple replating technique. From these comparative studies and other previous characterizations, it appears that a single gene mutation is responsible for the following pleiotropic phenotype: slow growth. UV sensitivity, high UV-induced mutability, high frequency of site-specific bromodeoxyuridine (BrdU)-dependent chromosome breaks and enhanced spontaneous mutation rate. Recent studies indicate that the mutation may be on the gene for DNA polymerase alpha. The results further indicate that thymidine auxotrophy or imbalance in nucleotide pools is not necessarily associated with the mutator activity in mammalian cells.

Animals↗
PubMed1982

Hypermutability of a UV-sensitive aphidicolin-resistant mutant of Chinese hamster fibroblasts.

An ultraviolet light (UV)-sensitive thymidine auxotroph of Chinese hamster V79 cells that exhibits pleiotropic effects such as a high level of deoxycytidine triphosphate, slow growth, sensitivity to cytidine, and high frequencies of site-specific bromodeoxyuridine-dependent chromosomal aberrations was selected by its resistance to aphidicolin. The UV-induced mutability of this mutant and one of its revertants, which retains some of the phenotypes listed above, was studied in 3 mutation assay systems. The results showed that the mutant was hypermutable for ouabain and diphtheria-toxin-resistant mutations compared to wild-type V79 cells at the same UV dose or the same survival level. The mutant exhibits a delayed expression of maximal frequency of induced 6-thioguanine-resistant mutants. When maximal frequencies are compared at the same UV dose, the mutant also has higher mutation frequencies at the hypoxanthine-guanine phosphoribosyl transferase locus. The revertant was similar to the wild-type in UV sensitivity and mutability. Our results showed that UV sensitivity and hypermutability are correlated and controlled by a single gene. Thymidine auxotrophy or nucleotide pool imbalance apparently did not contribute to the UV sensitivity and mutability of the mutant.

Animals↗
PubMed1982

Presynaptic toxicity of the histidine-modified, phospholipase A2-inactive, beta-bungarotoxin, crotoxin and notexin.

Beta-Bungarotoxin, crotoxin and notexin were treated extensively with p-bromophenacyl bromide in order to modify the histidine group of the active site and to greatly decrease the phospholipase A2(PLA) catalytic activity. They were studied for their residual presynaptic effects on the mouse isolated phrenic nerve-diaphragm and chick biventer cervicis muscle preparations. The modified toxins still had 1.7-5.2% PLA activity, which was inhibited by Sr2+, as is the enzyme activity of the native toxins. The neuromuscular blocking activity of these modified toxins, which was reduced 30-60 fold in the mouse diaphragm, was due to a presynaptic effect, as judged from the unchanged amplitude of m.e.p.p.s in the blocked preparations. In contrast to the native toxins, however, the presynaptic effect of modified beta-bungarotoxin and notexin was neither antagonized by Sr2+ nor accelerated by increasing the rate of nerve stimulation, indicating that the presynaptic effects of the modified beta-bungarotoxin and notexin are not likely to be due to their PLA enzyme activity. The modified toxins retained a much greater fraction of their early presynaptic effects in comparison to their enzymatic and neuromuscular blocking activities, although the time-course of the early effects was delayed. The results indicate that the modified neurotoxins per se have their own presynaptic effects, which are unrelated to the PLA enzyme activities.

Acetophenones↗