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Biomedical subjects

E H Chu

Publications and source records attributed to E H Chu.

At least 55 records · Page 3Linked to original sources
PubMed1977

Mutational approaches to the study of carcinogenesis.

A number of circumstantial lines of evidence are consistent with the somatic mutation theory of carcinogenesis, but there has been a paucity of experimental data that either support or contradict the genetic theory. In this paper, we summarize the predictions, the recent experimental approaches, and the problems involved in testing the theory. Results are presented that define the conditions and demonstrate the existence of two-stage processes of mutagenesis and carcinogenesis in vitro. We conclude that mutagenesis is responsible for the initiation of carcinogenesis and an epigenetic mechanism is responsible for its promotion. Carcinogenic agents can induce a stable transformation of a cell by either mutation or epigenetic alteration in gene expression. This conclusion has led us to propose a new integrative theory of carcinogenesis, encompassing the tenets of four main theories: (1) the mutation and epigenetic basis for carcinogenesis, (2) the two-stage theory of carcinogenesis, (3) a general theory of carcinogenesis, and (4) the somatic deletion mutation theory of carcinogenesis.

Animals↗
PubMed1977

Effect of phorbol myristate acetate on the recovery of spontaneous and ultraviolet light-induced 6-thioguanine and ouabain-resistant Chinese hamster cells.

12-0-Tetradecanoyl-phorbol-13-acetate (TPA) and phorbol were tested in Chinese hamster cells for their effects on mutagenesis (resistance to 6-thioguanine and to ouabain), DNA repair, and survival after ultraviolet (UV) irradiation. Recovery of 6-thioguanine- and ouabain-resistant colonies was significantly increased by TPA treatment and, to a lesser extent, by phorbol in UV-irradiated cells. Moreover, maximum enhancement of recoverable UV-induced 6-thioguanine- and ouabain-resistant mutants occurred when TPA was present after the mutation "expression" time and after the completion of DNA repair. This eenhancement effect, while persisting up to 18 days in the 6-thioguanine mutation system, was maximal when TPA was applied about 2 days after UV irradiation for the ouabain resistance mutation system. No significant decrease in cell survival was noted after post-UV treatment with TPA or phorbol, under conditions where there was a slight but nonspecific inhibition of unscheduled DNA repair synthesis. These results do not support the hypothesis that the tumor-promoting activity of TPA is due to its ability to inhibit "error-free" excision repair. The results are, however, consistent with a "two-stage" hypothesis of carcinogenesis which includes mutational and epigenetic mechanisms to explain the initiation and promotion phases.

Animals↗
PubMed1977

Cockayne syndrome: a cellular sensitivity to ultraviolet light.

Two unrelated children, a boy 2 1/2 years old and a girl 4 years old, were affected with the cachectic dwarfism of Cockayne syndrome. Fibroblast cultures derived from these patients exhibited increased sensitivity to ultraviolet (UV) light, but not to x-irradiation, as measured by colony-forming ability. In both Cockayne fibroblast cultures, the rate of removal of thymidine dimer from the irradiated cellular DNA was normal. This demonstration of a cellular defect in Cockayne cells suggests that there may be an enzymatic defect in the repair of UV light-induced damage.

Abnormalities, Multiple↗
PubMed1975

Mutant hamster cells exhibiting a pleiotropic effect on carbohydrate metabolism.

Sixty-seven galactose negative (Gal minus) clones were established from survivors after treatment of Chinese hamster lung (V79) cells with 5-bromodeoxyuridine and black light. The mutational origin of these clonal isolates was inferred on the basis of the previously demonstrated mutagenic action of the combined treatment, persistence of the Gal minus phenotype in cell progeny in the absence of selection, conditional lethality of three isolates, interallelic complementation, and assignment of a homologous human gene to chromosome A2. In contrast to the parental cells, Gal minus mutants could not utilize exogenous galactose, mannose, fructose, galactose 1-phosphate, glucose 1-phosphate, or glucose 6-phosphate. Permeation of galactose into mutant cells appeared unimpaired. In intra- and interspecific cell hybrids, the mutation causing the Gal minus phenotype behaved like a recessive character. The pleiotropic nutritional response was due not to deficiency of any one specific enzyme in the Leloir pathway but to significant reduction in activities of phosphoglucomutase, NADP-dependent isocitrate dehydrogenase, and perhaps other enzymes. In temperature-sensitive Gal minus mutants grown at permissive temperature or in complementing intra- and interspecific cell hybrids, the activities of these enzymes were restored to normal levels, accompanied by a regained ability to use the particular hexoses or hexose monophosphates. We postulate that the change from Gal + to Gal minus phenotype in hamster cells could be due to mutations at a regulatory gene locus, or at a yet unknown locus with enzymic defect that causes secondary metabolic imbalances.

Animals↗
PubMed1974

Chromosome assignment of the human gene for galactose-1-phosphate uridyltransferase.

Somatic cell hybrids formed between galactose-negative mutant Chinese hamster cells and human lymphocytes were selected in galactose medium and analyzed for the concurrent presence of specific human chromosome(s) and human galactose-1-phosphate uridyltransferase. In one of the hybrid clones only a single human chromosome, A2, was consistently present when the hybrid cells were maintained in the selective medium, suggesting that the location of the structural gene for galactose-1-phosphate uridyltransferase is on this chromosome. Among subclones derived from this cell hybrid in the absence of selection, a complete concordance was demonstrated between the ability or inability to utilize galactose and the concomitant presence or absence of the human transferase and the A2 chromosome.

Animals↗
PubMed1972

Induction of auxotrophic mutations by treatment of Chinese hamster cells with 5-bromodeoxyuridine and black light.

Treatment of an aneuploid Chinese hamster cell line (V79) in tissue culture with 5-bromodeoxyuridine and black light, with or without prior exposure of cells to another mutagen, led to the isolation of auxotrophic mutants, each of which exhibits a specific nutritional requirement for glycine, uridine, purine, or for a combination of glycine, hypoxanthine, and thymidine. 61 mutants that could not use exogenous galactose were also isolated. Thus, this treatment functions as an inductive, but not as a selective, procedure for mutations in mammalian cells.

Animals↗