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C S Tsao

Publications and source records attributed to C S Tsao.

At least 19 recordsLinked to original sources
PubMed1998

Growth suppression of malignant leukemia cell line in vitro by ascorbic acid (vitamin C) and its derivatives.

In recent years there has been a growing interest in the therapeutic application of L-ascorbic acid (AA) and its derivatives as anticancer agents. AA is a gamma-crotonolactone derivative with reactive hydroxyl groups at the 2- and 3-positions and an ethylene glycol substitution at the 4-position. Despite the various reports on AA toxicity, no work has been reported underlying the critical chemical structural features for its activity. The present study addresses this question. We tested in vivo, using malignant leukemia cell line P388D1, (i) L-AA and its isomers, (ii) substitution at the 2-position: -PO4, -SO4, O-Me, O-octadecyl, (iii) substitution at the 6-position: -PO4, -SO4, -palmitate, -stearate, (iv) substitution at the 2,6-position: dipalmitate, (v) 6-deoxy derivative: -Cl, -Br, -NH2 and (vi) dihydroxy gamma-crotonolactone with substitutions at the 4-position: -H, -CH3, -CH2-CH3 and -CH=CH2. L-AA and its isomers were very cytotoxic even at very low concentration. All 6-substituted and 6-deoxy derivatives were as toxic as AA. However, 2-substituted and 2,6-disubstituted AA derivatives were non-toxic. Interestingly, dihydroxy gamma-crotonolactone with or without substitution at the 5-position also exhibited toxicity. These results suggest that the underlying criterion for AA toxicity resides in dihydroxy gamma-crotonolactone moiety. Either substitution in the hydroxy groups or saturating the double bond render the molecule inactive.

Animals↗
PubMed1998

Cytotoxic effect of substitution at 2-, 6-, and 2,6-positions in ascorbic acid on malignant cell line.

In recent years L-ascorbic acid (AA) and its isomers have raised considerable interest as anticancer agents, although the mechanism has remained largely unknown. AA isomers are nearly identical in their physical and chemical properties but differ widely in their biological properties. AA, a lactone sugar, has a number of reactive positions, especially at 2- and 6-. Although there are a number of reports on the cytotoxic effect of AA and its isomers on malignant and nonmalignant cell lines, no work has been reported on the comparative effects of substitutions at these active sites. This study, then, investigates the comparative cytotoxicity of such substitutes on the malignant leukemia P388 cell line in culture. We tested a series of 2-, 6- and 2,6- disubstituted AA-derivatives, comprising the following: i) substitution at 2-position: -PO4, -SO4, O-Me, O-octadecyl; ii) substitution at 6-position: -PO4, -SO4, -palmitate, -stearate; and iii) substitution at 2,6-position: -dipalmitate. About 50,000 P388 cells/ml were incubated with and without AA derivatives in a final concentration of 1000, 500, 100, 10 and 1 microg/ml in triplicate and counted after 72 hrs. All 2-substituted and the 2,6-substituted AA derivatives tested were nontoxic and ineffective in preventing cell growth. In contrast, all 6-substituted AA derivatives were very toxic at all levels, even at the lowest concentration. These results suggest that substitution at 2-, 6- and 2,6-positions in AA have a different effect on toxicity. The 2-, and 2,6-substituted AA derivatives are stable compounds, resistant to hydrolysis which render them inactive. The cytotoxicity of the 6-substituted derivatives may be explained by one of the following mechanisms, yet to be explored: i) the hydrolysis rate may differ; or ii) the chemical structure itself may affect toxicity. Further studies are in progress to understand the mechanism.

Animals↗
PubMed1997

Ascorbic acid deficiency decreases the expression of CYP4A1 in liver microsomes of guinea pigs.

The cytochrome P-450 monooxygenase system plays a central role in the oxidation of a wide variety of structurally unrelated compounds. Its contribution is affected by nutritional and several other factors. Ascorbic acid (AA) deficiency decreases the content of cytochrome P-450 in liver microsomes of guinea pigs (GPs). Included in the group of cytochromes P-450 are the phenobarbital and 3-methylcholanthrene inducible moieties. In the present study the effect of AA status on another specific cytochrome P-450, CYP4A1, laurate omega-hydroxylase was investigated. Ascorbic acid may selectively increase or decrease certain forms of cytochromes. For four weeks adult male Hartley GPs were fed a diet containing 2.5 (Group I), 0.1 (Group II) and 0% (Group III) AA. The liver microsomes were isolated at this stage and cytochrome P-450 content was determined. Group III showed a significant decrease in cytochrome P-450 compared to groups I and II. They also showed a marked decrease in aminopyrine N-demethylase activity. The expression of CYP4A1 was evaluated using Western blot and anti-CYP4A1 antibody. Group III GPs showed a marked decrease in CYP4A1 expression. Groups I and II showed similar expression. This study demonstrates that CYP4A1, a specific cytochrome induced by hypolipidemic agents, is decreased by AA deficiency.

Animals↗
PubMed1993

Influence of cobalamin on the survival of mice bearing ascites tumor.

The effect of cobalamin (vitamin B12) on the survival time of mice bearing P388 leukemia has been examined. Among the three cobalamins studied, the enzymatically active derivatives, methylcobalamin and 5'-deoxyadenosylcobalamin, were able to significantly increase the survival time of mice implanted intraperitoneally with the tumor cells. The pharmaceutical form, cyanocobalamin, was not active. The antitumor activity of these cobalamins may be associated with their functions in metabolism.

Animals↗
PubMed1992

Preparation of an optimum mobile phase for the simultaneous determination of neurochemicals in mouse brain tissues by high-performance liquid chromatography with electrochemical detection.

A systematic method is described for the optimization of a mobile phase for the simultaneous determination of 24 neurochemicals consisting of catecholamine, serotonin, their precursors and metabolites and related materials. This mobile phase contained sodium acetate (0.04 M), citric acid (0.01 M), sodium chloride (0.0126 M), sodium octyl sulfate (91 mg/l), tetrasodium EDTA (50 mg/l) and 10% (v/v) methanol. When this optimum mobile phase was applied to the analysis of brain tissues of the Swiss male mouse, twelve neurochemicals were quantified in the free state: tyrosine, L-beta-3,4-dihydroxyphenylanine, dopamine, 3,4-dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylacetic acid, norepinephrine, 3-methoxy-4-hydroxyphenylglycol, DL-3,4-dihydroxymandelic acid, DL-4-hydroxy-3-methoxymandelic acid, serotonin, L-tryptophan, 5-hydroxyindole-3-acetic acid and DL-synephrine and normetanephrine, appearing as a fused peak. This fused peak was present on the chromatogram tracings of all the mouse brain tissues. The separable neurochemicals not found by this procedure in the Swiss male mouse tissues were DL-3,4-dihydroxyphenylglycol,5-hydroxytryptophan, epinephrine, DL-octopamine, metanephrine, deoxyepinephrine, homovanillyl alcohol, N-acetylserotonin, tyramine and 3-methyltyramine.

Animals↗
PubMed1991

Inhibiting effect of ascorbic acid on the growth of human mammary tumor xenografts.

The effect of ascorbic acid on the growth of a human mammary tumor in mice has been investigated using the 6-d subrenal capsule assay method. The results indicated that ascorbic acid administered in the drinking water significantly inhibited the growth of the tumor fragments implanted beneath the renal capsule of mice. Administration of a mixture of ascorbic acid and cupric sulfate orally or intraperitoneally significantly inhibited tumor growth in these mice, whereas neither alone was effective. These results support the hypothesis that certain oxidation or degradation products of ascorbic acid were active antineoplastic agents for the human mammary tumor studied. The activity of D-isoascorbic acid, an isomer of ascorbic acid, was similar to that of ascorbic acid. This suggests that the antitumor activity of ascorbic acid was not due to the metabolism of ascorbic acid as a vitamin, but due to its chemical properties.

Animals↗
PubMed1990

Intraoperative radiation of canine carotid artery, internal jugular vein, and vagus nerve. Therapeutic applications in the management of advanced head and neck cancers.

As a step in the application of intraoperative radiotherapy (IORT) for treating advanced head and neck cancers, preliminary information was obtained on the radiation tolerance of the canine common carotid artery, internal jugular vein, and vagus nerve to a single, high-dose electron beam. Both sides of the neck of eight mongrel dogs were operated on to expose an 8-cm segment of common carotid artery, internal jugular vein, and vagus nerve. One side of the neck was irradiated, using escalating doses of 2500, 3500, 4500, and 5500 cGy. The contralateral side of the neck served as the unirradiated control. At 3 and 6 months after IORT, one dog at each dose level was killed. None of the dogs developed carotid bleeding at any time after IORT. Light microscopic investigations using hematoxylin-eosin staining on the common carotid artery and internal jugular vein showed no consistent changes that suggested radiation damage; however, the Masson trichrome stain and hydroxyproline concentration of irradiated common carotid artery indicated an increase in the collagen content of the tunica media. Marked changes in the irradiated vagus nerve were seen, indicating severe demyelination and loss of nerve fibers, which appeared to be radiation-dose dependent. Four patients with advanced recurrent head and neck cancer were treated with surgical resection and IORT without any acute or subacute complications. The role of IORT as a supplement to surgery, external beam irradiation, and chemotherapy in selected patients with advanced head and neck cancer needs further exploration.

Animals↗
PubMed1990

Cytotoxic activity of cobalamin in cultured malignant and nonmalignant cells.

The cytotoxic effect of cobalamin (vitamin B12) on the growth of malignant and nonmalignant cell lines in culture has been examined. Among the four cobalamins studied, 5'-deoxyadenosylcobalamin, an enzymatically active derivative, was an effective cytotoxic agent. The data indicated that adenosylcobalamin seemed to act selectively on fast-growing malignant cells. Methylcobalamin was also effective at elevated concentrations. Cyanocobalamin was not toxic to all cell lines studied. Hydroxocobalamin at very high concentrations was able to slightly decrease growth of certain cell lines. The results support the hypothesis that the cytotoxic effect of cobalamin was associated with the metabolic activities of this vitamin at the cellular level. Also, cobalamin may be a potential antitumor agent.

Animals↗
PubMed1990

Effect of dietary ascorbic acid on heat-induced eye lens protein damage in guinea pigs.

The effect of large intake of dietary ascorbic acid on heat-induced eye lens protein damage has been studied. Male guinea pigs of the Hartley strain were used. Ascorbic acid was administered to the experimental animals in the drinking water. The mean daily ascorbic acid intakes for the control and experimental animals were 10 and 366 mg/kg body weight, respectively. The ascorbic acid level in the lens of the experimental animals was significantly higher than in the controls, but no differences in the content of water-soluble lens proteins were observed. When a solution of water-soluble protein was incubated at 60 degrees C, insoluble aggregates were formed. The loss of water-soluble proteins from the lens of the experimental animals was significantly less than that of the controls. The results indicated that large quantities of dietary ascorbic acid were able to protect lens constituents against heat-induced damage.

Animals↗
PubMed1990

Levels of minerals in serum and urine of guinea pigs following intraperitoneal administration of ascorbate.

The effect of ascorbic acid administration on the levels of urinary and serum mineral nutrients, Ca, Cu, Fe, K, Mg, Mn, Na and Zn in guinea pigs has been studied. Male guinea pigs received sodium ascorbate solution (equivalent to 1 g ascorbic acid/kg body weight/day) by intraperitoneal injection for 4 weeks. During the ascorbic acid treatment period, serum and urinary ascorbic acid rose markedly. The large quantities of ascorbic acid intake did not influence serum levels of all eight minerals studied when experimental values were compared with controls using the two-tailed Student's t-test. However, when the one-tailed t-test was used, serum copper and zinc levels of the experimental guinea pigs were significantly lower than their respective control values. Excepting sodium, derived from injected sodium ascorbate, no differences in daily urinary excretion of the other seven minerals were observed.

Animals↗
PubMed1989

Effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice.

The effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice has been studied. After the mice were on diets containing added ascorbic acid for two months, the activities of ascorbic acid synthesizing enzymes in the mouse liver homogenates were measured using L-gulono-gamma-lactone as a substrate. Exogenous ascorbic acid intake (0.5, 1 or 5% in the diet) was able to increase the concentration of ascorbic acid in the blood and to decrease the activities of ascorbic acid synthesizing enzymes in mouse liver. The results suggest that ascorbic acid synthesis was controlled by local regulatory mechanism or by the concentration of ascorbic acid in the hepatic portal blood. Ingestion of dietary erythorbic acid, a stereoisomer of ascorbic acid, had no effect on the activities of ascorbic acid synthesizing enzymes.

Animals↗
PubMed1989

Effect of dietary ascorbic acid on levels of serum mineral nutrients in guinea pigs.

The effect of dietary ascorbic acid on the serum mineral nutrients, Ca, Cu, Fe, K, Mg, Mn, Na and Zn in guinea pigs has been studied. Large amounts of ascorbic acid were administered to experimental animals in their drinking water. The daily ascorbic acid intake from the diet for the control animals was 10 mg/kg body weight. The mean ascorbic acid intakes for the two groups of experimental animals were 366 (37 times control) and 722 (72 times control) mg/kg body weight/day. In the ascorbic acid-treated animals, there was a significant increase in serum ascorbic acid levels in comparison with the controls. No substantial differences were observed in the body weights. The large quantities of dietary ascorbic acid did not influence serum levels of all eight minerals studied when the experimental and control values were compared using the two-tailed Student's t-test. However, serum level of copper in the guinea pigs ingesting a daily dose of 722 mg of ascorbic acid per kg body weight was slightly below control value when one-tailed Student's t-test was used.

Animals↗
PubMed1988

Urinary ascorbic acid levels following the withdrawal of large doses of ascorbic acid in guinea pigs.

Male guinea pigs received sodium ascorbate solution [equivalent to 1 g ascorbic acid/(kg body weight.d)] by intraperitoneal injection for 4 wk. During the ascorbic acid treatment period, plasma and urinary ascorbic acid levels rose markedly. Three weeks after the ascorbic acid treatment was withdrawn, mean urinary ascorbic acid levels were significantly lower than their corresponding basal levels. At both 2 and 5 wk after withdrawal of ascorbic acid treatment, mean plasma ascorbic acid levels were below normal. The results indicate that these animals had experienced a transient withdrawal effect after administration of large doses of ascorbic acid that lasted about 1 wk. This, in turn, indicates that the rate of ascorbic acid turnover was probably increased during treatment, and this effect persisted even after the ascorbic acid was withdrawn. Examination of data from each individual experimental animal revealed that the pattern of urinary ascorbic acid excretion after the withdrawal of large doses of ascorbic acid varied from animal to animal. Among the twelve experimental guinea pigs, seven had abnormally low urinary ascorbic acid levels 2-4 wk after the withdrawal of the large doses of ascorbic acid.

Animals↗
PubMed1987

Effect of dietary ascorbic acid intake on tissue vitamin C in mice.

The effect of graded levels of dietary ascorbic acid on blood and tissue ascorbic acid levels in mice has been studied. Six levels of dietary ascorbic acid (0, 0.076, 0.5, 1, 5 and 8%) were used. Plasma ascorbic acid rose as dietary ascorbic acid intake increased from 1 to 8%. Mice fed a diet with 5 or 8% added ascorbic acid had significantly higher levels of ascorbic acid in the heart, kidney, lung, muscle and spleen than did control mice fed an ascorbic acid-free diet. Mice fed a diet with 1% added ascorbic acid had elevated ascorbic acid levels in the heart, kidney, lung and spleen. No significant change was observed in ascorbic acid level in the brain, adrenal gland or leukocytes in any of the experimental groups. Ascorbic acid level in the eyes was only slightly higher in mice fed a diet containing 8% added ascorbic acid than in control mice. The observation that the kidney had the greatest increase in ascorbic acid content suggests that the kidney may be a very important organ not only in elimination but also in catabolism of this vitamin. A diet containing 0.5 or 0.076% added ascorbic acid did not significantly increase ascorbic acid content in any of the organs studied. Mice fed a diet with 0.076% added ascorbic acid had slightly, but statistically significantly, lower levels of ascorbic acid in the liver, lung, muscle and spleen that control mice. Mice fed a diet with 0.5% added ascorbic acid had a lower ascorbic acid content in the liver and muscle than the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of ascorbic acid on calcium elimination in humans.

The long-term and short-term influence of large oral doses of ascorbic acid on the urinary excretion of calcium has been investigated. In the first experiment, daily doses of a total of 10 g of ascorbic acid were administered to healthy human subjects. Daily urinary samples of these subjects were collected before and during the treatment, and calcium contents of these samples were measured. Among the 22 subjects, 19 experienced no significant changes in urinary calcium levels during the ingestion of ascorbic acid, one subject experienced an increase, two had a decline. These changes in urinary calcium levels were relatively small and were within the changes from consuming normal diets. In the second experiment, urinary samples of 46 healthy subjects were collected during a period of 8 hours after the ingestion of 2 g of ascorbic acid (33 times the U.S. RDA). A significant increase in mean urinary calcium excretion from 48.2 +/- 25.1 mg to 58.3 +/- 28.0 mg in the 8-h time period was observed. Mean urinary volume and phosphorus were unchanged. Calcium levels of the initially low excretors were significantly elevated while the change in urinary calcium levels of the initially high excretors was not statistically significant following the administration of ascorbic acid. The results suggest that ascorbic acid has a short-term effect on the regulation of the absorption and metabolism of calcium in humans.

Adult↗