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C Y Shi

Publications and source records attributed to C Y Shi.

At least 37 records · Page 2Linked to original sources
PubMed1995

Codon 249 mutation of the p53 gene is a rare event in hepatocellular carcinomas from ethnic Chinese in Singapore.

The present study characterised p53 mutations in 44 hepatocellular carcinomas (HCCs) from Chinese patients residing in a high-incidence area. Twelve point mutations (27%) were detected in tumour tissues using single-strand conformation polymorphism analysis followed by direct DNA sequencing. Remarkably, no mutations were observed at codon 249. This is in contrast to HCCs from other high HCC incidence areas with endemic aflatoxin exposures, in which codon 249 is a mutational hot spot. It is therefore suggested that risk factors other than dietary exposure to aflatoxin may contribute to the high HCC incidence in Singapore.

Adult↗
PubMed1995

Aflatoxin B1-induced 8-hydroxydeoxyguanosine formation in rat hepatic DNA.

A time- and dose-dependent increase in 8-hydroxydeoxyguanosine (8-OHdG) was observed in rat hepatic DNA after a single i.p. injection of aflatoxin B1 (AFB1). It was also found that pre-treatment with selenium or deferoxamine significantly reduced 8-OHdG level in AFB1-administered rats. In contrast, no reduction in 8-OHdG concentration was found in vitamin E-pre-treated rats. These results provide evidence that AFB1 causes oxidative DNA damage in rat liver, which may involve hydroxyl radicals as the initiating species. It is postulated that AFB1-induced oxidative DNA damage (8-OHdG formation) may constitute an important pathway in AFB1 hepatocarcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Evaluation of biomarkers for occupational exposure to benzene.

OBJECTIVE: To evaluate the relations between environmental benzene concentrations and various biomarkers of exposure to benzene. METHODS: Analyses were carried out on environmental air, unmetabolised benzene in urine, trans, trans-muconic acid (ttMA), and three major phenolic metabolites of benzene; catechol, hydroquinone, and phenol, in two field studies on 64 workers exposed to benzene concentrations from 0.12 to 68 ppm, the time weighted average (TWA). Forty nonexposed subjects were also investigated. RESULTS: Among the five urinary biomarkers studied, ttMA correlated best with environmental benzene concentration (correlation coefficient, r = 0.87). When urinary phenolic metabolites were compared with environmental benzene, hydroquinone correlated best with benzene in air. No correlation was found between unmetabolised benzene in urine and environmental benzene concentrations. The correlation coefficients for environmental benzene and end of shift catechol, hydroquinone, and phenol were 0.30, 0.70, and 0.66, respectively. Detailed analysis, however, suggests that urinary phenol was not a specific biomarker for exposure below 5 ppm. In contrast, ttMA and hydroquinone seemed to be specific and sensitive even at concentrations of below 1 ppm. Although unmetabolised benzene in urine showed good correlation with atmospheric benzene (r = 0.50, P < 0.05), data were insufficient to suggest that it is a useful biomarker for exposure to low concentrations of benzene. The results from the present study also showed that both ttMA and hydroquinone were able to differentiate the background level found in subjects not occupationally exposed and those exposed to less than 1 ppm of benzene. This suggests that these two biomarkers are useful indices for monitoring low concentrations of benzene. Furthermore, these two metabolites are known to be involved in bone marrow leukaemogenesis, their applications in biological monitoring could thus be important in risk assessment. CONCLUSION: The good correlations between ttMA, hydroquinone, and atmospheric benzene, even at concentrations of less than 1 ppm, suggest that they are sensitive and specific biomarkers for benzene exposure.

Air Pollutants, Occupational↗
PubMed1995

Inhibition of aflatoxin B1-induced cell injury by selenium: an in vitro study.

Dietary selenium is an essential trace element in human nutrition. Selenium has been shown in animal studies to inhibit aflatoxin hepatocarcinogenesis. However, the cellular mechanism responsible for the inhibition has not been thoroughly studied. This study examines the effect of two selenium compounds, namely, sodium selenite and selenium-enriched yeast extract (SeY), on the cytotoxicity, DNA-binding and mutagenicity of aflatoxin B1 (AFB1) in cultured Chinese hamster ovary (CHO) cells. CHO cells, after treatment with 2 micrograms ml-1 selenite or 80 micrograms ml-1 SeY, exhibited increased resistance to AFB1-induced cell killing. At a concentration of 50 micrograms ml-1 AFB1, cell survival, measured by the clonogenicity assay, was increased by 21- and 10-fold in selenite- and SeY-treated cells, respectively. However, selenium treatment did not appear to affect AFB1-DNA binding. Similarly, no effect was observed on AFB1 mutagenicity, as determined by the hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene mutation assay. The results showed that selenium could effectively protect cells from AFB1 cytotoxicity in cultured cells but had no effect on AFB1-DNA adduct formation or mutagenesis. It is suggested that there are multiple pathways of AFB1 toxicity and that selenium can modulate AFB1-induced cell killing independent of its genotoxicity.

Aflatoxin B1↗
PubMed1995

Mutations of the tumour suppressor gene p53 in colorectal and hepatocellular carcinomas.

The present study describes mutations of the tumour suppressor gene p53 in a local collection of colorectal and hepatocellular carcinomas (HCCs). Tumour DNA was extracted from both fresh and paraffin-embedded tissues and exons 5-8 of the p53 gene were amplified by polymerase chain reaction (PCR). Mutations were detected by single-strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing. Of the 38 colorectal carcinomas and 42 HCCs examined, 15 (39%) and 13 (31%), respectively, showed p53 mutations. Two-thirds (10/15) of the mutations in colorectal carcinomas were base transitions with a predominance at CpG dinucleotide sites--a pattern characteristic to an endogenous process in cancer development. Three mutational hotspots at codons 175, 248 and 282 were also identified. Mutations did not correlate with histological grade, Dukes stage, or metastasis. However, tumours at the distal site of the colorectum showed a higher proportion of mutations than the proximal site. In the case of HCCs, majority (9/13) of the mutations were base transitions and no mutations were observed at codon 249. This is in contrast to results from other high-incidence areas such as Africa and China, where aflatoxin is believed to be a major aetiologic factor for liver cancers. The results therefore suggest that other risk factors, rather than dietary exposure to aflatoxin, may contribute to the high HCC incidence in Singapore.

Adenocarcinoma↗
PubMed1994

Elevated levels of benzene-related compounds in the urine of cigarette smokers.

Benzene exposure causes leukemia and lymphomas. Recent epidemiological findings have also shown an association between cigarette smoking and an increased risk of leukemia. However, further evidence is required to document the biological plausibility of this association. In evaluating this link, it is important to note that cigarette smoke contains benzene and various pyrolytic compounds, among other carcinogens. This study aims to determine the uptake of benzene by measuring 3 benzene-related compounds in cigarette smokers and non-smokers. Urinary concentrations of catechol (CAT), hydroquinone (HQ), and trans,trans-muconic acid (tt-MA) were measured by high-performance liquid chromatography (HPLC) with fluorimetric and UV detection, respectively. The results showed that these compounds were present in all urine samples. However, the concentrations were significantly higher in smokers than in non-smokers. The mean level of urinary tt-MA was 0.19 +/- 0.09 mg/g creatinine for 46 male smokers and the corresponding value for 40 non-smokers was 0.14 +/- 0.07 mg/g creatinine. The mean concentrations of HQ and CAT were 0.81 +/- 0.4 and 3.51 +/- 2.6 mg/g creatinine for smokers, and 0.45 +/- 0.4 and 1.94 +/- 1.2 mg/g creatinine for non-smokers, respectively. These results suggest that cigarette smoking is associated with a significant additional exposure to benzene and its related compounds. Furthermore, significant correlations were observed between the concentrations of cotinine, the metabolite of nicotine, and the above compounds. These findings suggest that the exposure originated from cigarette smoking.

Benzene Derivatives↗
PubMed1994

Inhibition of aflatoxin B1-DNA binding and adduct formation by selenium in rats.

The effect of selenium on aflatoxin B1-DNA binding and adduct formation was studied. Male Fischer 344 rats, fed with up to 8 ppm of sodium selenite in drinking water for 8 weeks, were given a single i.p. dose of aflatoxin B1. The rats were killed 24 h later and the amount of AFB1 bound to hepatic DNA and the amount of DNA adducts formed were determined. Selenium pretreatment resulted in a dose-dependent inhibition of AFB1-DNA binding as well as adduct formation. This was accompanied by an increase of reduced glutathione (GSH) in the liver of selenium-treated animals. These results suggest that selenium could effectively inhibit AFB1-induced DNA damage, which may be partially responsible for its anticarcinogenic effect against AFB1.

Aflatoxin B1↗
PubMed1994

Biological monitoring of exposure to low concentrations of styrene.

A field study was conducted on 39 male workers exposed to styrene at concentrations below 40 ppm (time weighted average, TWA). Analyses were carried out on environmental air, exhaled air, blood, urine, and two major urinary metabolites of styrene: mandelic acid (MA) and phenylglycoxylic acid (PGA). Head space gas chromatography (GC) with a flame ionization detector (FID) was used for determination of styrene in blood and urine. Postexposure exhaled air was analyzed using capillary GC. Environmental styrene exposure was measured by personal sampling using carbon cloth personal samplers. Urinary metabolites of styrene were determined by high pressure liquid chromatograph (HPLC). When the end-of-shift breath, blood, and urine styrene levels were compared with environmental TWA values, blood styrene correlated best with styrene in air (r = 0.87), followed by breath styrene (r = 0.76). Poor correlation (r = 0.24) was observed between environmental styrene exposure and urine styrene. When styrene metabolites were compared with environmental styrene, the sum of urinary MA and PGA correlated better with styrene in air than MA or PGA alone. The correlations between urinary metabolites and environmental styrene improved when corrected for the specific gravity of urine. Even better correlations were observed when the urinary metabolites were corrected for creatinine. The correlation coefficients for environmental styrene and end-of-shift MA, PGA, and MA+PGA were 0.83, 0.84, and 0.86, respectively. The correlation coefficients between environmental styrene and next morning urinary metabolites fell to 0.47, 0.61, and 0.65 for MA, PGA, and MA+PGA, respectively. These results suggest that determination of the total MA and PGA in urine samples is preferred than separate measurements of MA or PGA. The good correlation between environmental exposure and styrene in the exhaled air also suggests that breath styrene level can be a useful indicator for low level styrene exposure, as the method is specific, noninvasive, and rapid. Urinary styrene seems to be a less reliable indicator for low level styrene exposure.

Adult↗
PubMed1994

Aflatoxin B1-induced lipid peroxidation in rat liver.

Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin. The mechanism of cellular damages caused by AFB1 has not been fully elucidated. Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenesis of many carcinogens. In this study, we investigated the induction of lipid peroxidation by AFB1 in the liver of Fischer 344 rats. Malonaldehyde (MDA) and conjugated dienes, both products of lipid peroxidation, were determined in liver homogenate and subcellular fractions. An increase of MDA and conjugated dienes in liver homogenate was detected 1 day after AFB1 administration. It reached the peak level 3 days after dosing and remained at an elevated level up to 14 days. The induction of MDA by AFB1 was also found to be dose-dependent. Measurements of lipid peroxidation in the subcellular fractions revealed that microsomes had the highest concentration of MDA, followed by those of the nuclear fraction and mitochondria. MDA concentration was not detectable in the cytosolic fraction. Further, it was found that pretreatment with selenium and vitamin E, both antioxidants, and deferoxamine, a specific iron chelator, significantly inhibited lipid peroxidation as well as liver cell damage. These results provide in vivo evidence that AFB1 can cause lipid peroxidation in rat liver. Oxidative damages caused by AFB1 may be one of the underlining mechanisms for AFB1-induced cell injury and DNA damage, which eventually lead to tumorigenesis.

Aflatoxin B1↗
PubMed1994

Kinetics of styrene urinary metabolites: a study in a low-level occupational exposure setting in Singapore.

Biological monitoring of styrene exposure commonly involves measurement of styrene metabolites, mainly mandelic acid (MA) and phenylglyoxylic acid (PGA), in the urine of exposed subjects. Previous studies on the kinetics of styrene metabolites in urine were mostly conducted in a controlled environment on subjects exposed to high concentrations of styrene. In this study, we examined subjects exposed to low levels of styrene in a fiber-reinforced plastics (FRP) plant to see whether the excretion kinetics of styrene metabolites are similar under field conditions. Eight healthy Chinese male volunteers were exposed to styrene for 4 h with a mean environmental concentration of 11 ppm. Urine samples were collected continuously for 20 h after termination of the exposure and concentrations of urinary MA and PCA were determined. The results showed that MA was rapidly excreted in urine after the exposure, with a half-life of 2.1 h or 1.9 h when corrected with urine creatinine. The excretion of PGA followed that of MA and the half-life was 8.1 h or 5.1 h after correction with creatinine. The half-lives are considerably shorter compared to those in previous reports, suggesting that environmental factors, exposure conditions, or ethnic differences may affect the excretion kinetics of styrene metabolites. The fast excretion of styrene metabolites is also consistent with the observation that urine MA and PGA levels correlated better with the half-day time-weighted average (TWA) concentration of environmental styrene than with the whole-day TWA concentration. Our findings thus underscore the need for information on excretion kinetics in order to develop an appropriate biological monitoring scheme for specific exposure settings and subjects.

Adult↗
PubMed1994

Amplification of cDNA via RT-PCR using RNA extracted from postmortem tissues.

Analysis of cDNA derived from messenger RNA is of advantage over using genomic DNA in genetic analysis of large genes, especially those with lengthy intron sequences. However, because of its instability and rapid degradation, RNA extraction from postmortem tissues has not been attempted. Here, we report the successful extraction of intact mRNA from various postmortem tissues from accidental and sudden death cases. Subsequently with reverse transcriptase-polymerase chain reaction (RT-PCR), we were able to amplify cDNA fragments of different lengths up to 0.9 kb. The described method therefore provides a useful tool in genetic analysis of postmortem tissues.

Base Sequence↗
PubMed1993

Simultaneous determination of hydroquinone, catechol and phenol in urine using high-performance liquid chromatography with fluorimetric detection.

A method was developed for simultaneous determination of urinary hydroquinone, catechol and phenol using high-performance liquid chromatography (HPLC) with variable-wavelength fluorimetric detection. Urine samples, after acid hydrolysis, were saturated with sodium sulphate and extracted by diethyl ether. The two buffers used for gradient elution were (A) 10 mM sodium acetate containing 0.5% (v/v) acetic acid and (B) the same as buffer A but containing an additional 20% (v/v) acetonitrile. Hydroquinone, catechol and phenol were separated in a C18 column and detected at 2.9, 6.8 and 13.6 min, respectively. The recovery and reproducibility were generally over 90%. Over 300 extracted samples were analysed and no change in column efficiency was noted. Comparisons were also made with HPLC using ultraviolet (UV) detection and with gas chromatography (GC). The proposed method appears to be more sensitive and reliable than other existing methods. This new method was also validated with urine samples collected from cigarette smokers and from refinery workers exposed to low concentrations of benzene.

Animals↗
PubMed1993

Urinary trans,trans-muconic acid determined by liquid chromatography: application in biological monitoring of benzene exposure.

We describe a sensitive and specific high-performance liquid-chromatographic method for determining the benzene metabolite, trans,trans-muconic acid (ttMA) in urine by measuring ultraviolet absorbance at 265 nm. We mix 1 mL of urine sample with 2 mL of Tris buffer containing vanillic acid as internal standard (IS) and percolate this through a preconditioned ion-exchange column. After rinsing the column with phosphoric acid solution, acetate buffer, and deionized water, we elute the analytes with 2 mL of an equivolume solution of 1.5 mol/L sodium chloride and methanol. Of this, 5 microL is injected into the HPLC column. The mobile phase used consists of, per liter, 10 mL of acetic acid, 100 mL of methanol, and the rest 5 mmol/L sodium acetate. The flow rate was started at 1 mL/min and increased to 1.5 mL/min after 6 min. ttMA and IS were detected at 5.2 and 10.2 min, respectively. The lowest detection limit is 125 pg. Analytical recovery and reproducibility generally exceeded 90%. We validated the method with urine samples collected from normal persons and from refinery workers exposed to benzene concentrations < 1 microL/L. The results show that urinary ttMA is a promising biological marker for risk assessment of low-concentration benzene exposure.

Benzene↗
PubMed1991

Percutaneous transaortic closure of postinfarctional ventricular septal rupture.

We report a case of successful closure of a postinfarctional ventricular septal defect by means of the transaortic approach with a balloon catheter. This method brought about substantial improvement in cardiopulmonary function before an elective operation and made it possible to successfully perform the operation on the patient, an 81-year-old woman, on the 22nd day of admission.

Aged↗
PubMed1990

Uptake of mercury by the hair of methylmercury-treated newborn mice.

Human hair has unique advantages in monitoring environmental exposures to methylmercury. Using newborn Balb/c mice as a model system, the incorporation of methylmercury into the hair was studied and compared with methylmercury distributions in other tissues. Newborn mice were given intraperitoneal injections of 203Hg-labeled methylmercury at designated times according to hair growth stages of the mouse. Animals were sacrificed 2 days after dosing. Distribution of mercury in pelt and other tissues was measured. The level of mercury in pelt was found to correlate with hair growth. The amount of mercury in pelt peaked when hair growth was most rapid and the total amount of mercury in pelt was significantly higher than that in other tissues, constituting 40% of the whole body burden. However, when the hair ceased growing, the amount of mercury in pelt dramatically dropped to 4% of whole body burden and mercury concentrations in other tissues except brain were elevated. Autoradiographic studies with tritium-labeled methylmercury demonstrated that methylmercury concentrated in hair follicles in the skin. Within hair follicles and hairs, methylmercury accumulated in regions that are rich in high-sulfur proteins. The uptake of inorganic mercury (administered as HgCl2) by pelt was also compared with that of methylmercury. The amount of inorganic mercury found in pelt was less than one-half that of methylmercury in animals with growing hair. Cessation of hair growth did not decrease the inorganic mercury level in pelt to the same extent as in the case of methylmercury.

Animals↗
PubMedDate not supplied

Cytotoxicity and DNA strand breaks induced by benzene and its metabolites in Chinese hamster ovary cells.

The cytotoxicity of benzene (BZ) and its major metabolites phenol (PHE), hydroquinone (HQ), catechol (CAT), 1,4-benzoquinone (BQ), 1,2,4-benzenetriol (BT), trans,trans-muconic acid (ttMA) and S-phenylmercapturic acid (S-PMA) was assessed by exposing Chinese Hamster Ovary (CHO) cells to these compounds. Benzene was the least toxic (LD50 = 20 mM), while BQ showed the highest potency (LD50 = 10 microM), followed by HQ (LD50 = 40 microM). It was found that the trend of cytotoxicity was: BQ > HQ > > CAT > ttMA > BT > S-PMA > > PHE > BZ. 1,4-Benzoquinone and HQ also demonstrated considerable ability to induce DNA strand breaks in CHO cells, which was assayed using the fluorimetric analysis of DNA unwinding. The other metabolites were unable to cause DNA strand breaks. When HQ was administered in combination with other metabolites, no synergism was observed in the induction of DNA strand breaks. From these results, it can be seen that BQ and HQ are the most bioreactive species among the benzene metabolites when tested on CHO cells. Differences between the results obtained in our study and other studies were discussed.

Animals↗