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C Y Shi

Publications and source records attributed to C Y Shi.

At least 19 recordsLinked to original sources

Use of the VIP-Man model to calculate energy imparted and effective dose for x-ray examinations.

A male human tomographic model was used to calculate values of energy imparted (epsilon) and effective dose (E) for monoenergetic photons (30-150 keV) in radiographic examinations. Energy deposition in the organs and tissues of the human phantom were obtained using Monte Carlo simulations. Values of E/epsilon were obtained for three common projections [anterior-posterior (AP), posterior-anterior (PA), and lateral (LAT)] of the head, cervical spine, chest, and abdomen, respectively. For head radiographs, all three projections yielded similar E/epsilon values. At 30 keV, the value of E/epsilon was approximately 1.6 mSv J(-1), which is increased to approximately 7 mSv J(-1) for 150 keV photons. The AP cervical spine was the only projection investigated where the value of E/epsilon decreased with increasing photon energy. Above 70 keV, cervical spine E/epsilon values showed little energy dependence and ranged between approximately 8.5 mSv J(-1) for PA projections and approximately 17 mSv J(-1) for AP projections. The values of E/epsilon for AP chest examinations showed very little variation with photon energy, and had values of approximately 23 mSv J(-1). Values of E/epsilon for PA and LAT chest projections were substantially lower than the AP projections and increased with increasing photon energy. For abdominal radiographs, differences between the PA and LAT projections were very small. All abdomen projections showed an increase in the E/epsilon ratio with increasing photon energy, and reached a maximum value of approximately 13.5 mSv J(-1) for AP projections, and approximately 9.5 mSv J(-1) for PA/lateral projections. These monoenergetic E/epsilon values can generate values of E/epsilon for any x-ray spectrum, and can be used to convert values of energy imparted into effective dose for patients undergoing common head and body radiological examinations.

Adult↗

Specific absorbed fractions for internal photon emitters calculated for a tomographic model of a pregnant woman.

Specific absorbed fractions are essential for calculation of radiation dose from internal emitters. Existing specific absorbed fractions for pregnant women were calculated using the stylized models; in this work, a partial-body tomographic model for a pregnant woman was constructed from a rare set of CT images. Based on this tomographic model, the Monte Carlo code, EGS4-VLSI, was used to derive specific absorbed fractions. Monoenergetic, isotropic photon emitters from 15 keV to 4 MeV were distributed in different source organs, and doses were calculated to many target regions in the body. Even though the results showed general agreement with previous studies for higher energies, significant differences were also found, especially for lower energies. The main reasons for the differences are due to the variation of mass, geometry, and organ distances, and they demonstrate the influence of more realistic body models on dose calculations.

Adult↗

Colorectal carcinoma among ethnic Chinese in Singapore: trends in incidence rate by anatomic subsite from 1968 to 1992.

BACKGROUND: Recent epidemiologic studies have suggested that the anatomic distribution of colorectal carcinoma may have undergone a distal to proximal shift over several decades, which has been attributed variously to environmental and genetic factors as well as preventive intervention. METHODS: Trends in subsite distribution and the incidence rate of colorectal carcinoma among Chinese in Singapore between 1968 and 1992 were explored using data from the Singapore Cancer Registry (n = 10,489). Age-standardized incidence rates were computed and compared further using age-period-cohort models by subsite and gender. RESULTS: The proportion of lesions in the distal colon was found to have increased from 23.2% to 24.4% whereas that for the proximal colon and rectum were fairly consistent over the past 25 years. Our results also showed that age-standardized rates have doubled in proximal lesions (2-3% annually) and more than doubled in distal lesions (3-4% annually) whereas rates in rectal carcinoma have shown a slight increase or stability over time. The patterns of change in all subsite tumors could be attributed to a significant birth cohort effect. CONCLUSIONS: The results of the current study suggest that incidence rates have increased rapidly with no distal to proximal shift observed among ethnic Chinese in Singapore over the past 25 years. The pattern of change differs from findings reported in high incidence countries such as the U. S. and parts of Europe, suggesting that the preventive intervention and early diagnostic capabilities that may have played an important role in these countries have had less effect in Asia. The rapid overall increase in the incidence rate of colon carcinoma supports the role of dietary and other environmental factors as possible risk factors.

Adult↗

HPLC analysis of isoflavonoids and other phenolic agents from foods and from human fluids.

A fast, precise and selective diode array HPLC method is presented for the extraction and analysis of soy isoflavonoids from foods and from human urine, plasma, and breast milk in support of mechanistic and epidemiologic studies assessing the potential cancer protective role of soya or isoflavones. Solid phase or solvent extraction was chosen for isolation, and enzymatic or acid hydrolysis procedures were used for aglycone production depending on the matrix to be analyzed. C-18 reversed-phase HPLC was applied to selectively separate and quantitate daidzein (1), glycitein (3), and genistein (4), including their malonyl (a) and acetyl (b) esters, and their mammalian metabolites equol (6) and O-desmethylangolensin (7), as well as formononetin (2), biochanin-A (5), and coumestrol (8) using a gradient elution system. UV absorbance scans and authentic standards were applied for identification purposes, additional to fluorometric monitoring, electrochemical detection, and GC/ MS analysis after trimethyl silylation. Detection limits of 20-microl injections were found to be 1.09, 0.53, 3.28, and 1.00 pmoles for daidzein, genistein, equol, and O-desmethylangolensin (DMA), respectively, by monitoring at the individual compound's absorption maximum. The proposed method was applied to monitor isoflavone levels in soy foods and in human plasma, urine and breast milk after challenge with roasted soybeans. Implications of the presented results on the potential activity of isoflavones to prevent cancer by exposing newborn infants to these agents are discussed.

Chromatography, High Pressure Liquid↗

Isoflavonoid levels in spot urine are associated with frequency of dietary soy intake in a population-based sample of middle-aged and older Chinese in Singapore.

Soy products contain high amounts of isoflavonoids, which have been shown to exhibit possible cancer-protective properties. Chinese populations in Asia, in particular, have a high level of soy intake and a relatively low risk of hormone-dependent cancers. In this study, we assessed the distributions of dietary soy isoflavonoids (daidzein, genistein, and glycitein) and urinary soy isoflavonoids and their metabolites (daidzein, genistein, glycitein, equol, and O-desmethylangolensin) among 147 Singapore Chinese (76 men and 71 women) ages 45-74 years, who are participants of the Singapore Cohort Study on diet and cancer. Urinary values were measured from spot samples collected 10-20 months following recruitment, when usual dietary habits were assessed by a structured food frequency/portion size questionnaire administered in person. Dietary levels of daidzein and genistein were comparable within individuals and about seven times higher than the level of dietary glycitein. All three dietary isoflavonoids showed an approximately 3.5-fold difference between the 25th and 75th percentile values. Similarly, daidzein was the most abundant and glycitein the least abundant of the five isoflavonoid compounds in urine. There was a 4.9-fold difference between the 25th and 75th percentile values for the sum of the five urinary isoflavonoids. Among study subjects, there were statistically significant, dose-dependent associations between frequency of overall soy intake and levels of urinary daidzein (two-sided P = 0.03) and sum of urinary daidzein, genistein, and glycitein (two-sided P = 0.04). In contrast, there were no associations between frequency of overall soy intake and levels of the two daidzein metabolites (equol and O-desmethylangolensin) in urine (two-sided P = 0.85 and 0.34, respectively). We suggest that within the range of exposures experienced by Singapore Chinese, urinary level of daidzein or the sum of daidzein, genistein, and glycitein obtained from a spot sample can serve as a biomarker of current soy consumption in epidemiological studies of diet-disease associations.

Aged↗

Urinary total isothiocyanate (ITC) in a population-based sample of middle-aged and older Chinese in Singapore: relationship with dietary total ITC and glutathione S-transferase M1/T1/P1 genotypes.

Isothiocyanates (ITCs), degradation products of glucosinolates (which occur naturally in a variety of cruciferous vegetables), have been shown to exhibit chemopreventive activity. These compounds are metabolized in vivo to form the corresponding dithiocarbamates, which are the major urinary metabolites of ITCs, by a pathway involving the glutathione S-transferase (GST) class of enzymes. Using a newly developed assay that measures total ITC (primarily ITC conjugates) in urine, we examined the relationships between cruciferous vegetable intake (obtained from a food frequency/portion size questionnaire administered in person); dietary total ITC level; GSTM1, GSTT1, and GSTP1 genotypes; and levels of total ITC in spot urine samples collected from 246 Singapore Chinese (111 men and 135 women), ages 45-74 years, who are participants of the Singapore Cohort Study on diet and cancer. Consumption level of cruciferous vegetables was high in study subjects (mean consumption = 345 times per year, mean daily intake = 40.6 g), which was >3 times the comparable level of intake in the United States. Mean daily intake of total ITC among study subjects was 9.1 micromol, and there was a 2.5-fold difference between the 25th and 75th percentile values. Seventy-three % of study subjects tested positive for ITC in urine, and there was a 4-fold difference between the 25th and 75th percentile values among the positive subjects. There was a highly significant positive association between dietary intake and urinary excretion levels of total ITC (two-sided P = 0.0003) that was stronger than the association between overall cruciferous vegetable intake and urinary ITC level, which also was statistically significant (P = 0.0004). There was no difference in urinary ITC levels between GSTM1-null and GSTM1-positive study subjects (P = 0.61) or between subjects with differing GSTP1 genotypes (P = 0.77), but urinary excretion of ITC was significantly higher among GSTT1-positive subjects, relative to GSTT1-null subjects (P = 0.006). The strength of the association between GSTT1 genotype and urinary total ITC level was highly dependent on the level of cruciferous vegetable consumption (or dietary ITC level) in study subjects. Among subjects in the lowest tertile of cruciferous vegetable intake, there was little evidence of an association between GSTT1 genotype and urinary total ITC level (P = 0.67). In contrast, there was a strong and statistically significant association between GSTT1 genotype and urinary total ITC among subjects in the highest tertile of cruciferous vegetable intake (P = 0.02), whereas those in the middle tertile of cruciferous vegetable consumption exhibited an association of intermediate strength (P = 0.04). These results suggest the presence of GSTT1 inducers in cruciferous vegetables.

Age Factors↗

Genetic variation of 3 beta-hydroxysteroid dehydrogenase type II in three racial/ethnic groups: implications for prostate cancer risk.

BACKGROUND: Elevated prostatic dihydrotestosterone (DHT) has been suggested to increase the risk of prostate cancer. The HSD3B2 gene encodes the type II 3 beta-hydroxysteroid dehydrogenase: one of two enzymes that initiate the inactivation of DHT. Thus, the HSD3B2 gene is a candidate gene for predisposition to prostate cancer. METHODS: We have determine the distribution of a complex dinucleotide repeat in the HSD3B2 gene in high-risk African-Americans, intermediate-risk Euro-Americans, and low-risk Asians. Genomic DNA from 312 individuals was amplified by polymerase chain reaction (PCR) and analyzed by electrophoresis on denaturing polyacrylamide gels. RESULTS: We have found that certain alleles are either unique to or much more common in either African-Americans, Asians, or Euro-Americans. Our data also substantially expand the number of alleles reported for the complex dinucleotide repeat polymorphism in the HSD3B2 gene. CONCLUSIONS: Our report demonstrates substantial genetic variation in the HSD3B2 gene. We hypothesize that allelic variants of the HSD3B2 gene may play a role in predisposition to prostate cancer, and in explaining the substantial racial/ethnic variation in risk.

3-Hydroxysteroid Dehydrogenases↗

A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase.

Prostate cancer is the most common serious cancer diagnosed in men in the United States. This disease is also characterized by a striking racial/ethnic variation in incidence: highest in African-Americans, intermediate in Caucasians, slightly lower in Latinos, and lowest in Asians. Ample biochemical and epidemiological evidence suggests a role for androgens, particularly testosterone and dihydrotestosterone, in prostate cancer etiology. We have analyzed a candidate gene for prostate cancer, SRD5A2, encoding prostatic steroid 5alpha-reductase type II, which converts testosterone into the more bioactive dihydrotestosterone, for mutations. We report here one amino acid substitution, V89L, which replaces valine at codon 89 with leucine. This substitution is a "germline" (constitutional) DNA polymorphism, and it is common, panethnic, and reduces in vivo steroid 5alpha-reductase activity. This substitution is particularly common among Asians and may explain the low risk for prostate cancer in this population.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies.

Markers in the 3' end of the vitamin D receptor gene have recently been associated with prostate cancer risk. To evaluate the adequacy of the commonly used BsmI restriction fragment length polymorphism as a marker of this locus, we genotyped 627 individuals from five ethnic groups for this marker, as well as for a polymorphic site in the 3' untranslated region of this gene. At the latter site, we identified 12 alleles, A13 to A24, of a poly(A) microsatellite. Allele size followed a bimodal distribution with distinct short (A13-A17) and long (A18-A24) allele populations. Poly(A) allele frequency differed by ethnicity, with the frequency of short alleles being highest in non-Hispanic whites (41%), intermediate in Hispanics and African-Americans (31 and 29%, respectively), and lowest in Japanese-Americans and Chinese (8 and 9%, respectively). In each of the ethnic groups, some degree of coupling was observed between BsmI B and short poly(A) alleles and between BsmI b and long poly(A) alleles. However, the strength of the linkage disequilibrium varied by ethnicity, with departures from complete disequilibrium producing disagreement between the BsmI and poly(A) genotypes. Genotypic disagreement was lowest in Japanese-Americans and non-Hispanic whites (6 and 7%, respectively), intermediate in Chinese and Hispanics (11 and 19%, respectively), and highest among African-Americans (37%), indicating that BsmI is not a good marker for the vitamin D receptor 3' untranslated region genotype in all populations. This finding may explain contradictory results from recent association studies using the BsmI marker.

Asian↗

Increased iron in the substantia nigra of 6-OHDA induced parkinsonian rats: a nuclear microscopy study.

The trace elemental concentrations, including iron, in the substantia nigra (SN) of a 6-OHDA induced rat model of Parkinson's disease were measured using nuclear microscopy. Only rats that exhibited amphetamine induced rotation of more than 7 turns/min were used. The results showed that the iron levels were significantly increased in the 6-OHDA lesioned SN, compared with the intact contralateral SN, and the SN of normal control rats injected with ascorbic acid, which showed no significant difference in iron levels between injected and non-injected sides. In both 6-OHDA lesioned and ascorbic acid injected SN, there were no alterations in the levels of calcium, magnesium, copper and zinc. In the 6-OHDA lesioned SN there was an almost complete loss of tyrosine hydroxylase positive cells in the SN. These results suggested that the 6-OHDA induced dopaminergic cell death may be related to the increased iron.

Animals↗

Detection of elevated reactive oxygen species level in cultured rat hepatocytes treated with aflatoxin B1.

Accumulating evidence demonstrates that oxidative damage is one of the underlying mechanisms to the cytotoxicity and carcinogenicity of AFB1. The main objective of this study is to show that AFB1 increases reactive oxygen species (ROS) formation in hepatocytes. The ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescin diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS. It was found that AFB1 exposure significantly enhanced DCF fluorescence formation in cultured rat hepatocytes. A dose-response of AFB1 was also observed within the range of 10 nM to 1000 nM. Catalase (CAT) was able to completely prevent the increase of DCF fluorescence in AFB1-treated cells in a dose-dependent manner (from 500 to 2000 U/ml). Moreover, the significant inhibitory effects of desferrioxamine (DFO) and dimethyl sulfoxide (DMSO) on DCF fluorescence formation were also observed in both control and AFB1-treated hepatocytes. Therefore, results from the present study provide in vitro evidence indicating the generation of ROS in cultured rat hepatocytes caused by AFB1 exposure. It is postulated that the metabolic process of AFB1 by cytochrome P450 might be the possible source of the elevated ROS level in AFB1-treated hepatocytes. The enhanced level of ROS may be responsible for the oxidative damage caused by AFB1, which may ultimately contribute to the cytotoxic and carcinogenic effects of AFB1.

Aflatoxin B1↗

Determination of heterocyclic amines in flame-grilled fish patty by capillary electrophoresis.

A simple and reliable capillary zone electrophoretic (CZE) method for quantifying mutagenic and carcinogenic heterocyclic amines (HCAs) in cooked foods with UV-visible diode-array detection is described. The buffer system consisted of 50 mM disodium hydrogen phosphate, 30 mM sodium chloride, 20 mM citric acid and 26% methanol at pH 2.1. An uncoated silica tubing, 51 cm in length, was used for the CZE separation. The capillary tubing temperature was maintained at 25 degrees C with a constant voltage of 20 kV. The reproducibility of the method was over 95% for a five-replicate analysis of 10 micrograms/l-spiked 2-amino-3,4,7,8-tetramethylimidazo[4,5-f]quinoxaline (4,7,8-TriMeIQx) and the detection limit was in the low microgram/l range with coefficients of variation between 6 and 18%. An analytical run took only 15 min for 12 known HCAs. Using this procedure, up to 30 samples could be analysed in a single day. The method is reliable and can be used for screening of various HCAs. It has been applied to assess the concentrations of heterocyclic amines in otak-otak, a Malay-style grilled fish patty. The major mutagenic contaminant found in this foodstuff was 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) (286-1068 micrograms/kg), followed by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (1.6-13.0 micrograms/kg) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) (14.0-87.5 micrograms/kg). Two co-mutagens norharman (NH) and harman (H) were also detected in otak-otak at levels of 2.0-13.0 micrograms/kg and 12.8-21.3 micrograms/kg, respectively. The substantial amount of Glu-P-2 detected in otak-otak is probably a result of the ingredients used and the high temperature grilling process.

Amines↗

Biomarkers of exposure to low concentrations of benzene: a field assessment.

OBJECTIVE: To carry out a comprehensive field investigation to evaluate various conventional and recently developed biomarkers for exposure to low concentrations of benzene. METHODS: Analyses were carried out on environmental air, unmetabolised benzene in blood and urine, urinary trans, transmuconic acid, and three major phenolic metabolites of benzene: phenol, catechol, and hydroquinone. Validations of these biomarkers were performed on 131 never smokers occupationally exposed to the time weighed average benzene concentration of 0.25 ppm (range, 0.01 to 3.5 ppm). RESULTS: Among the six biomarkers studied, unmetabolised benzene in urine correlated best with environmental benzene concentration (correlation coefficient, r = 0.76), followed by benzene in blood (r = 0.64). When urinary metabolites were compared with environmental benzene, trans, trans-muconic acid showed a close correlation (r = 0.53) followed by hydroquinone (r = 0.44), and to a lesser extent with urinary phenol (r = 0.38). No correlation was found between catechol and environmental benzene concentrations. Although unmetabolised benzene in urine correlates best with benzene exposure, owing to serious technical drawbacks, its use is limited. Among the metabolites, trans, trans-muconic acid seems to be more reliable than other phenolic compounds. Nevertheless, detailed analyses failed to show that it is specific for monitoring benzene exposures below 0.25 ppm. CONCLUSION: The overall results suggest that most of the currently available biomarkers are unable to provide sufficient specificity for monitoring of low concentrations of benzene exposure. If a lower occupational exposure limit for benzene is to be considered, the reliability of the biomarker and the technical limitations of measurements have to be carefully validated.

Air↗

Benzene metabolites enhance reactive oxygen species generation in HL60 human leukemia cells.

Benzene is myelotoxic and leukemogenic in humans. The mechanisms leading to these effects, however have not been fully elucidated. One of the underlying mechanisms is believed to be the oxidative damage caused by its metabolites. A comparative study was undertaken to examine the relationships between reactive oxygen species (ROS) production, lipid peroxidation and subsequent cytotoxicity induced by five major benzene metabolites. The generation of ROS by benzene metabolites was demonstrated by the significant and dose-dependent increase of intracellular ROS formation in HL60 human promyelocytic leukemia cells in vitro. 1,4-Benzoquinone (BQ) was found to be the most potent metabolite in induction of ROS formation, followed by 1,2,4-benzenetriol (BT) and to a lesser extent, phenol (PH) and trans, trans-muconaldehyde (MD). No significant effect was observed when the cells were treated with trans, trans-muconic acid (MA). The enhancement of ROS production by BQ was effectively inhibited by the addition of catalase, deferoxamine (DFO) and dimethyl sulfoxide (DMSO), but unchanged by superoxide dismutase (SOD), suggest that hydrogen peroxide (H2O2) and hydroxyl radicals (OH) are the two major forms of ROS involved. The results also demonstrate that the ability of benzene metabolites in enhancing ROS generation is closely correlated to their capacity in causing lipid peroxidation and subsequent cytotoxicity. These findings together with earlier parallel observations on DNA damage suggest that ROS play an important role in the mechanism of carcinogenesis induced by benzene metabolites.

Aldehydes↗

Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma.

Aberrations of the p53 and Rb tumour suppressor genes were examined in 12 human hepatocellular carcinoma (HCC)-derived cell lines from different geographic areas and 9 local HCCs by restriction fragment length polymorphisms (RFLP), polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and DNA sequencing. The relationships between genetic changes and hepatitis B virus (HBV) DNA integration in samples were compared. None of the cell lines and tumours showed structural changes in the Rb gene, while 6 cell lines and 2 tumours had mutation or deletion in exons 5 to 8 of p53. Mutations include an AGG --> AGT (Arg --> Ser) transversion at codon 249 in PLC/PRF/5 and Mahlavu, an AAT --> AAA (Asn --> Cys) transversion at codon 200 in TONG/HCC, an AAG --> GAG (Lys --> Glu) transition at codon 139 in HCC-T, a CAT --> CGT (His --> Arg) transition at codon 214 in SC4, and a CCC --> CTC (Pro --> Leu) transition at codon 250 in SC8. In Huh4, an 18-bp deletion from codon 264 to 270 resulted in loss of Leu-Gly-Arg-Asn-Ser-Phe from the amino acid sequences 265 to 270, whereas Hep3B had a 7-kb deletion after exon 7 of p53. Our data indicate that whereas Rb may not have pleiotropic effects on HCC, p53 aberrations are frequently involved in hepatocarcinogenesis. Further, HBV infection appears to be unrelated to the micro-genetic changes of p53. The G to T codon-249-mutation is consistent with HCCs arising from areas at high risk for both aflatoxin B1 (AFB1) exposure and HBV infection.

Animals↗

Biomarkers: a molecular approach to cancer epidemiology.

The rapidly evolving field of molecular epidemiology represents a paradigm shift in medical research, illustrating the convergence of basic, clinical and epidemiologic research, as well as the application of laboratory methods to population studies. As a complement and improvement to traditional epidemiologic approaches, the use of biomarkers offers more accurate exposure assessment at an individual level, better understanding of the biological mechanism of carcinogenesis by tracking a continuum of events between exposure and disease, as well as the ability to discern host or genetic factors that may account for variations in cancer susceptibility among individuals or ethnic populations. Further, biomarkers have also proved useful in cancer diagnosis and prognosis. This article attempts to review the latest progress in molecular cancer epidemiology and to summarise the current state of research in Singapore.

Biomarkers, Tumor↗

Molecular epidemiology: issues in study design and statistical analysis.

Traditional analytical epidemiology is directed at identifying the association between risk factors and occurrence of disease by using crude exposure data derived from questionnaires or clinical measures, and taking clinical disease as the end point. With the rapid development in molecular biology and laboratory methods, it is now possible to use biomarkers which are capable of identifying molecular events for epidemiologic research. This improved sensitivity enables us to develop a mechanistic understanding of disease causation: a step closer to the unravelling of the "black box" of traditional epidemiology. Biomarkers may be classified as internal indicators of exposure (biomarkers of exposure), indicators of preclinical adverse effect (biomarkers of effect) or indicators of an intrinsic or acquired susceptibility to disease (biomarkers of susceptibility). Biomarkers provide a better definition of exposure and disease status and consequently they could help to reduce misclassification bias in both exposure and disease, reduce the follow-up time in prospective studies, as well as identify possible interactions between risk factors on disease occurrence. However, a biomarker needs to be validated and its distribution in large populations described before it can be used profitably for aetiologic research. Also, the use of biomarkers in epidemiologic research raises other interesting epidemiological and statistical issues like confounding, effect modification and the analysis of repeated measurements. Molecular epidemiology is a multidisciplinary endeavour which comprises molecular biology, epidemiology and biostatistics. Clearly then, to carry out research in this field profitably, the molecular biologist, epidemiologist and biostatistician must acquire not only expertise in their respective fields, but also an integrated understanding of all three fields. The molecular biologist is not merely a laboratory bench worker; the epidemiologist, a field data-collector and the biostatistician, a number cruncher. They must work together to pry open the "black box" to gain a greater insight into how risk factors operate to initiate disease onset and ultimately to make use of this knowledge base to implement preventive measures.

Biomarkers↗

Involvement of reactive oxygen species in aflatoxin B1-induced cell injury in cultured rat hepatocytes.

The role of reactive oxygen species (ROS) in AFB1-induced cell injury was investigated using cultured rat hepatocytes. Malonaldehyde (MDA) generation and lactate dehydrogenase (LDH) release were determined as indices of lipid peroxidation and cell injury, respectively. Exposure to AFB1 for up to 72 h resulted in significantly elevated levels of LDH being released into the medium as well as the MDA generation in cultured hepatocytes. These effects were dose-dependent, indicating that AFB1 was capable of inducing oxidative damages in the cell. Further, MDA generation and LDH release were effectively inhibited by the addition of the following: (1) superoxide dismutase (500 units/ml), (2) catalase (1500 units/ml), (3) 10 mM desferrioxamine (a specific iron chelator), or (4) 260 mM dimethyl sulfoxide (a hydroxyl radical scavenger). These evidences therefore suggest that ROS, such as superoxide radicals, hydroxyl radicals and hydrogen peroxides, are involved in AFB1-induced cell injury in cultured rat hepatocytes.

Aflatoxin B1↗