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Biomedical subjects

C C Chang

Publications and source records attributed to C C Chang.

At least 667 records · Page 37Linked to original sources
PubMed1978

Effects of harman and norharman on spontaneous and ultraviolet light-induced mutagenesis in cultured Chinese hamster cells.

Nontoxic concentrations of harman and norharman were tested in cultured Chinese hamster cells for their effects on DNA repair and mutagenesis. The following effects of harman were observed: (a) the survival of ultraviolet light- or X-ray-damaged cells was reduced; (b) the ultraviolet light-induced unscheduled DNA synthesis was slightly inhibited; and (c) the frequency of spontaneous or ultraviolet light-induced ouabain-resistant (ouar) or 6-thioguanine-resistant (6-TGr) mutations was reduced. Furthermore, the effect of harman on survival and mutagenesis was greater than that of norharman and was detected primarily in treatments in which cells were exposed to harman immediately following ultraviolet light irradiation. Our data clearly indicate that harman decreases the capacity to repair DNA damage and fix mutations in Chinese hamster cells, possibly because of the intercalation properties of this compound.

Alkaloids↗
PubMed1977

Effects of Sr2+ and Mg2+ on the phospholipase A and the presynaptic neuromuscular blocking actions of beta-bungarotoxin, crotoxin and taipoxin.

1.beta-Bungarotoxin, crotoxin and taipoxin, presynaptic neurotoxins of snake venom origin, have about the same phospholipid-splitting activities as a much less toxic cobra phospholipase A2 in the presence of Ca2+ and deoxycholate. 2. Sr2+ was a much less effective activator of the enzymes than is Ca2+, the activation by Sr2+ being only 3-6% for beta-bungarotoxin and crotoxin and 12% for taipoxin. 3. Sr2+ also inhibited the Ca2+ -activated enzymes by 80% in the cases of beta-bungarotoxin and crotoxin, but only 16% in the case of taipoxin. 4. Mg2" had no significant effect on beta-bungarotoxin or crotoxin, but activated taipoxin in the presence or absence of Ca2". 5. In Sr2+ -Tyrode lacking Ca2+ all three toxins exhibited the same immediate depression followed by facilitation in the rat and mouse diaphragms, but the final blocking activity was only 3-10% with beta-bungarotoxin and crotoxin and was 30% with taipoxin. 6. In Sr2+ -Tyrode, increasing in the rate of nerve stimulation had less accelerating effect on the development of neuromuscular block than in Ca2+ -Tyrode for any of the toxins. 7. Removal of Mg2+ from Sr2+ -Tyrode did not diminish the potency of taipoxin in blocking neuromuscular transmission, suggesting that enzyme activity at the outer surface of the axolemma does not contribute to the neuromuscular blocking action. 8. All of the results indicate that there are close correlations between the presynaptic activities of these toxins and their phospholipid-splitting activities in the cationic environment prevailing in the axoplasm. Apparently the final blocking effect of these toxins is due to phospholipase A action within the nerve terminal.

Animals↗
PubMed1977

Mutagenic and epigenetic influence of caffeine on the frequencies of UV-induced ouabain-resistant Chinese hamster cells.

Caffeine, given as a post-treatment to UV-irradiated Chinese hamster cells in vitro, modified the frequency were increased when caffeine was added only for the DNA repair and mutation fixation period. When caffeine was added after the DNA repair and mutation fixation period, or immediately after DNA damage and for the entire repair and selection period, mutation frequencies were reduced. A hypothesis, given to explain both results, is that caffeine, by blocking a constitutive "error-free" postreplication repair process, allows an "error-prone" DNA repair process to produce many mutations. Moreover, caffeine, possibly by modifying C-AMP metabolism, causes a repression of induced mutations which, in effect, explains its anti-mutagenic and anti-carcinogenic properties.

Caffeine↗
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↗
PubMed1976

An analysis of the mode of action of carbachol on the chick biventer cervicis nerve--muscle preparation.

The mechanism of contracture evoked by carbachol in the isolated chick biventer cervicis nerve--muscle preparation was studied. At concentrations lower than 11 muM, carbachol progressively induced contracture at a rate much slower than did acetylcholine. A spontaneous increase of the response to carbachol, but not to acetylcholine, was observed 2-4 hr after isolation of the muscle. By contrast, no change of the response occurred in the denervated muscle. Anticholinesterase treatment shifted the dose-response curve for carbachol markedly to the left as far as the contracture attained after 4-6 min incubation was concerned. The shift was much less marked for the dose-response curve plotted against the initial rate of response defined as the contracture obtained after 1 min incubation. No enhancement of response was detected by inhibition of acetylcholinesterase in the denervated muscle. beta-Bungarotoxin which blocked neuromuscular transmission within 30 min, caused a transient enhancement of the response to carbachol. After 2-3 hr treatment, however, the spontaneous increase of response to carbachol was counteracted by the toxin. No potentiation of the response by anticholinesterase agents was observed after toxin treatment. When added in the presence of physostigmine or echothiophate, beta-bungarotoxin reduced the response to carbachol to the control level in 2 hr. The response to carbachol in the muscle treated with alpha-bungarotoxin and washed subsequently was also not potentiated by anticholinesterase treatment. Repetitive nerve stimulation in the presence of hemicholinium-3 caused a neuromuscular blockade but did not appreciably antagonize the response to carbachol more than that to acetylcholine either in the absence or presence of physotigmine. When calcium ion in the medium was decreased from 2.7 to 0.54 mM, ther response to nerve stimulation was nearly completely inhibited, but the response to carbachol was not affected and could still be potentiated by anticholinesterase. It is concluded that carbachol has both direct and indirect effects on the chick biventer cervicis muscle. At a low concentration, particularly in the presence of an anticholinesterase and if sufficient time of incubation is allowed, the indirect effect caused by release of acetylcholine may become more prominent than the direct action on the post-synaptic receptor. Both the mechanism and the store of acetylcholine for this indirect action appear to be different from those for the nerve impulse.

Acetylcholine↗