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Ching-Quo Wong

Bio: Ching-Quo Wong is an academic researcher from La Roche College. The author has contributed to research in topics: Mutation frequency & Ames test. The author has an hindex of 9, co-authored 10 publications receiving 1350 citations.

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Journal Article
TL;DR: The effects of topically applied curcumin, chlorogenic acid, caffeic acid, or ferulic acid on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ornithine decarboxylase activity, epidersmal DNA synthesis, and the promotion of skin tumors were evaluated in female CD-1 mice.
Abstract: The effects of topically applied curcumin, chlorogenic acid, caffeic acid, and ferulic acid on 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ornithine decarboxylase activity, epidermal DNA synthesis, and the promotion of skin tumors were evaluated in female CD-1 mice. Topical application of 0.5, 1, 3, or 10 µmol of curcumin inhibited by 31, 46, 84, or 98%, respectively, the induction of epidermal ornithine decarboxylase activity by 5 nmol of TPA. In an additional study, the topical application of 10 µmol of curcumin, chlorogenic acid, caffeic acid, or ferulic acid inhibited by 91, 25, 42, or 46%, respectively, the induction of ornithine decarboxylase activity by 5 nmol of TPA. The topical application of 10 µmol of curcumin together with 2 or 5 nmol of TPA inhibited the TPA-dependent stimulation of the incorporation of [ 3 H]-thymidine into epidermal DNA by 49 or 29%, respectively, whereas lower doses of curcumin had little or no effect. Chlorogenic acid, caffeic acid, and ferulic acid were less effective than curcumin as inhibitors of the TPA-dependent stimulation of DNA synthesis. Topical application of 1, 3, or 10 µmol of curcumin together with 5 nmol of TPA twice weekly for 20 weeks to mice previously initiated with 7,12-dimethylbenz[ a ]anthracene inhibited the number of TPA-induced tumors per mouse by 39, 77, or 98%, respectively. Similar treatment of mice with 10 µmol of chlorogenic acid, caffeic acid, or ferulic acid together with 5 nmol of TPA inhibited the number of TPA-induced tumors per mouse by 60, 28, or 35%, respectively, and higher doses of the phenolic acids caused a more pronounced inhibition of tumor promotion. The possibility that curcumin could inhibit the action of arachidonic acid was evaluated by studying the effect of curcumin on arachidonic acid-induced edema of mouse ears. The topical application of 3 or 10 µmol of curcumin 30 min before the application of 1 µmol of arachidonic acid inhibited arachidonic acid-induced edema by 33 or 80%, respectively.

779 citations

Journal Article
TL;DR: Treatment of the animals with the green tea extract not only decreased the number of skin tumors but also decreased substantially the size of the tumors.
Abstract: Green tea was prepared by extracting 12.5 g of green tea leaves twice with 500 ml of boiling water, and the extracts were combined. This 1.25% green tea extract (1.25 g of tea leaves/100 ml of water) contained 4.69 mg of green tea extract solids per ml and was similar in composition to some green tea beverages consumed by humans. A 2.5% green tea extract (2.5 g of tea leaves/100 ml of water) was prepared similarly. Treatment of female SKH-1 mice with 180 mJ/cm2 of ultraviolet B light (UVB) once daily for 7 days resulted in red sunburn lesions of the skin. The intensity of red color and area of these lesions were inhibited in a dose-dependent fashion by the administration of 1.25 or 2.5% green tea extract as the sole source of drinking water before and during UVB treatment. Treatment of female SKH-1 mice with 180 mJ/cm2 of UVB once daily for 10 days followed 1 wk later by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate for 25 wk resulted in the development of skin tumors. The formation of skin tumors was inhibited by administration of 1.25% green tea extract as the sole source of drinking water prior to and during the 10 days of UVB treatment and for 1 wk after UVB treatment. In additional experiments, female SKH-1 mice were treated with 200 nmol of 7,12-dimethylbenz(a)anthracene followed 3 wk later by irradiation with 180, 60, or 30 mJ/cm2 of UVB twice weekly for 30 wk. UVB-induced formation of skin tumors and increased spleen size were inhibited by administration of 1.25% green tea extract as the sole source of drinking water prior to and during the 30 wk of UVB treatment. In these experiments, treatment of the animals with the green tea extract not only decreased the number of skin tumors but also decreased substantially the size of the tumors. In additional studies, SKH-1 mice were initiated by topical application of 200 nmol of 7,12-dimethylbenz(a)anthracene followed by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate for 25 wk. Administration of 1.25% green tea extract as the sole source of drinking water during promotion with 12-O-tetradecanoylphorbol-13-acetate reduced the number and incidence of skin tumors.

272 citations

Journal Article
TL;DR: Results indicated that decreasing the dose of (+)-BPDE decreased the proportion of mutations at GC base pairs and increased the proportion at AT base pairs, and dose-dependent differences in (+)- BPDE-induced exon deletions and hot spots for base substitutions at GC and AT base Pair were indicated.
Abstract: Chinese hamster V-79 cells were exposed to a high dose (0.30–0.48 µm; 32% cell survival), an intermediate dose (0.04–0.10 µm; 100% cell survival) or a low dose (0.01–0.02 µm; 97% cell survival) of (+)-7 R ,8 S -dihydroxy-9 S ,10 R -epoxy-7,8,9,10-tetrahydrobenzo( a )pyrene [(+)-BPDE] which is the ultimate carcinogenic metabolite of benzo( a )pyrene. The mutation frequency for cells treated with dimethyl sulfoxide vehicle or with low, intermediate or high doses of (+)-BPDE were 1, 10, 52 or 514 8-azaguanine-resistant colonies/105 survivors, respectively. Independent 8-azaguanine-resistant clones were isolated, and complementary DNAs were prepared by reverse transcription. The coding region of the hypoxanthine (guanine) phosphoribosyltransferase ( HPRT ) gene was amplified by the polymerase chain reaction and sequenced. Altogether, 368 (+)-BPDE-induced mutant clones were examined. At all doses, base substitutions were the most prevalent mutations observed (about 72% of the mutant clones), followed by exon deletions (about 26% of the mutant clones) and frame-shift mutations (about 6% of the mutant clones). At the high cytotoxic dose, 7 of 120 base substitutions occurred at AT base pairs (6%) and 113 at GC base pairs (94%). At the intermediate noncytotoxic dose, 20 of 82 base substitutions occurred at AT base pairs (24%) and 62 at GC base pairs (76%). At the low noncytotoxic dose, 27 of 76 base substitutions were at AT base pairs (36%) and 49 were at GC base pairs (64%). The results indicated that decreasing the dose of (+)-BPDE decreased the proportion of mutations at GC base pairs and increased the proportion of mutations at AT base pairs. As the dose of (+)-BPDE was decreased, there was a dose-dependent decrease in the proportion of GC→TA transversions (from 69% to 42% of the base substitutions) and a dose-dependent increase in the proportion of AT→CG transversions (from 1% to 25% of the base substitutions). The data also indicated dose-dependent differences in (+)-BPDE-induced exon deletions and hot spots for base substitutions at GC and AT base pairs. Although more than 99% of the (+)-BPDE-induced mutations at guanine occurred on the nontranscribed strand of DNA, (+)-BPDE-induced mutations at adenine occurred on both the transcribed and nontranscribed strands. The ratio of mutations at adenine on the transcribed strand to mutations at adenine on the nontranscribed strand was 35:19 in (+)-BPDE-treated V-79 cells. These observations suggest different mechanisms of mutation induction at GC and AT base pairs and/or differences in repair mechanisms for premutagenic lesions at GC and AT base pairs. Several nucleotide sequences with frequent (+)-BPDE-induced mutations targeted at guanines in the coding region of the HPRT gene were identified. These included AGGGGGGC, TGGA, AGGA, TGGT, AGGC, TGGGA, AGGGA, and TGGGGA. Seventy % of all base substitution mutations targeted at guanine were on these sequences. (+)-BPDE-induced mutations in ras motifs (corresponding to ras codons 12, 13, 61) in the coding region of the HPRT gene were more commonly observed than by chance.

90 citations

Journal ArticleDOI
TL;DR: There was a trend towards an increase in the proportion of mutations at AT base pairs when the dose of (-)-BPDE was decreased, but this trend was not statistically significant and the data indicated no dose-dependent differences in the kinds of base substitutions or exon deletions in cDNAs induced by (-)- BPDE.
Abstract: Earlier studies from our laboratories characterized the mutation profile of the optically active (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-BPDE--the ultimate carcinogenic metabolite of benzo[a]pyrene] in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene of Chinese hamster V-79 cells. In the present study, we evaluated the mutation profile of (-)-7S,8R-dihydroxy-9R, 10S-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(-)-BPDE-a weakly carcinogenic or inactive enantiomer] and compared its mutation profile with that of (+)-BPDE. In both diol epoxide enantiomers, the benzylic 7-hydroxy group and epoxide oxygen are trans. The mutation frequency for V-79 cells treated with DMSO vehicle or with a low, non-cytotoxic dose (0.5 microM) or a high cytotoxic dose (2.0 microM) of (-)-BPDE was 1, 25 or 185 8-azaguanine-resistant colonies/10(5) survivors, respectively. Independent 8-azaguanine-resistant clones were isolated, and complementary DNAs were prepared by reverse transcription. The coding region of the HPRT gene was amplified by the polymerase chain reaction and sequenced. Altogether, 92 (-)-BPDE-induced mutant clones were examined. At both doses, base substitutions were the most prevalent mutations observed (present in approximately 7% of the mutant clones), followed by exon deletions (present in approximately 22% of the mutant clones) and frame shift mutations (present in approximately 6% of the mutant clones) in the cDNAs analyzed. At the high cytotoxic dose, 5 out of 36 base substitutions occurred at AT base pairs (14%) and 31 at GC base pairs (86%). At the low, non-cytotoxic dose, 7 out of 34 base substitutions were at AT base pairs (21%) and 27 were at GC base pairs (79%). Although there was a trend towards an increase in the proportion of mutations at AT base pairs when the dose of (-)-BPDE was decreased, this trend was not statistically significant. The data also indicated no dose-dependent differences in the kinds of base substitutions or exon deletions in cDNAs induced by (-)-BPDE. Ninety-one per cent of the (-)-BPDE-induced mutations that occurred at guanine were on the non-transcribed strand of DNA and 9% were on the transcribed strand. In contrast to these results, 50% of the (-)-BPDE-induced mutations that occurred at adenine were on the transcribed strand and 50% on the non-transcribed strand.(ABSTRACT TRUNCATED AT 400 WORDS)

60 citations

Journal Article
TL;DR: The carcinogenic effect of several dose levels and regimens of an aqueous solution of N-methyl-N-nitrosourea (MNU) administered intrarectally to mice and rats is reported in this paper.
Abstract: Summary The carcinogenic effect of several dose levels and regimens of an aqueous solution of N-methyl-N-nitrosourea (MNU) administered intrarectally to mice and rats is reported. In Ha/ICR Swiss mice, a single dose of 1.8 mg MNU induces mainly lymphomas and pulmonary tumors in less than 20 weeks. Repeated doses of 1.5 mg MNU induces lymphomas, pulmonary tumors, and also large bowel tumors in less than 20 weeks. Doses of 0.3 mg decreased the yield of lymphomas and increased large bowel neoplasms over a period of 40 to 60 weeks. Repeated doses of 0.06 mg also gave a low yield of lymphomas and large bowel tumors over a 60-week period. Thus, a maximal yield of lymphomas is seen with a brief regimen of high doses, whereas large bowel tumors occur with a more frequent lower dose rate. Male Fischer strain rats given 1.0 or 2.5 mg MNU 3 times a week for 10 weeks had a multiplicity of large bowel tumors, proportional to dose, in 25 to 30 weeks. In fact, the high dose level led to a 100% yield in less than 20 weeks. Lymphomas were seen only at the higher dose when the animals were young, at the beginning of the test. In mice and rats the carcinomas were polypoid or plaque shaped and were well differentiated with extensive invasion but no metastases. The adenomas were pedunculated or sessile. Intrarectal administration of a mixture of methylurea and nitrite for 20 weeks and further observation of the rats for an additional 35 weeks yielded no colon tumors. Thus, there is indirect evidence of a lack of the in situ formation of carcinogenic MNU in the large bowel under physiological conditions.

56 citations


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TL;DR: Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis, and Pharmacologically,Curcumin has been found to be safe.
Abstract: Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF- κB, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies. Curcumin, derived from turmeric (vernacular name: Haldi), is a rhizome of the plant Curcuma longa. The medicinal use of this plant has been documented in Ayurveda (the Indian

2,453 citations

Journal ArticleDOI
TL;DR: Curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin", a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis.

1,897 citations

Journal ArticleDOI
TL;DR: The aim of this review is to summarize and analyze the vast and sometimes conflicting literature on tannins and to provide as accurately as possible the needed information for assessment of the overall effects of tannin effects on human health.
Abstract: Tannins (commonly referred to as tannic acid) are water-soluble polyphenols that are present in many plant foods. They have been reported to be responsible for decreases in feed intake, growth rate, feed efficiency, net metabolizable energy, and protein digestibility in experimental animals. Therefore, foods rich in tannins are considered to be of low nutritional value. However, recent findings indicate that the major effect of tannins was not due to their inhibition on food consumption or digestion but rather the decreased efficiency in converting the absorbed nutrients to new body substances. Incidences of certain cancers, such as esophageal cancer, have been reported to be related to consumption of tannins-rich foods such as betel nuts and herbal teas, suggesting that tannins might be carcinogenic. However, other reports indicated that the carcinogenic activity of tannins might be related to components associated with tannins rather than tannins themselves. Interestingly, many reports indicated negative association between tea consumption and incidences of cancers. Tea polyphenols and many tannin components were suggested to be anticarcinogenic. Many tannin molecules have also been shown to reduce the mutagenic activity of a number of mutagens. Many carcinogens and/or mutagens produce oxygen-free radicals for interaction with cellular macromolecules. The anticarcinogenic and antimutagenic potentials of tannins may be related to their antioxidative property, which is important in protecting cellular oxidative damage, including lipid peroxidation. The generation of superoxide radicals was reported to be inhibited by tannins and related compounds. The antimicrobial activities of tannins are well documented. The growth of many fungi, yeasts, bacteria, and viruses was inhibited by tannins. We have also found that tannic acid and propyl gallate, but not gallic acid, were inhibitory to foodborne bacteria, aquatic bacteria, and off-flavor-producing microorganisms. Their antimicrobial properties seemed to be associated with the hydrolysis of ester linkage between gallic acid and polyols hydrolyzed after ripening of many edible fruits. Tannins in these fruits thus serve as a natural defense mechanism against microbial infections. The antimicrobial property of tannic acid can also be used in food processing to increase the shelf-life of certain foods, such as catfish fillets. Tannins have also been reported to exert other physiological effects, such as to accelerate blood clotting, reduce blood pressure, decrease the serum lipid level, produce liver necrosis, and modulate immunoresponses. The dosage and kind of tannins are critical to these effects. The aim of this review is to summarize and analyze the vast and sometimes conflicting literature on tannins and to provide as accurately as possible the needed information for assessment of the overall effects of tannins on human health.

1,687 citations

Journal ArticleDOI
TL;DR: Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer’s disease.
Abstract: Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its complex chemistry as well as its ability to influence multiple signaling pathways, including survival pathways such as those regulated by NF-κB, Akt, and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and exhibits both pro- and antioxidant activity. It also binds metals, particularly iron and copper, and can function as an iron chelator. Curcumin is remarkably non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer’s disease.

1,599 citations

Journal ArticleDOI
TL;DR: This review summarizes the most interesting in vitro and in vivo studies on the biological effects of curcumin, the constituent of turmeric, which has been widely studied for its anti-inflammatory, anti-angiogenic,Anti-oxidant, wound healing and anti-cancer effects.

1,526 citations