Does aflatoxin B1 play a role in the etiology of hepatocellular carcinoma in the United States?

Previous research showed that risk factors associated with hepatocellular carcinoma (HCC) include infection with hepatitis B (HBV) and hepatitis C (HCV) viruses, exposure to aflatoxin B1 (AFB1), and liver cirrhosis, due primarily to alcohol consumption. To determine whether AFB1 may play a role in HCC in the United States, a search for AFB1 adducts and p53 alterations, potentially induced by AFB1, was conducted in the United States in 23 HCC patients with available tissue samples. The presence of AFB1 tumor-DNA and -serum lysine adducts and mutant p53 product was determined by immunoassays and codon 249 p53 mutation by restriction enzyme analysis. HBV and HCV serology and serum HBV-DNA were also determined. Thirteen patients were positive for HBV by HBs antigen or anti-HBc antigen or by polymerase chain reaction for HBV-DNA sequences. Nine patients were free of HBV and HCV markers; 5 of 22 sera tested were anti-HCV positive. p53 Protein expression, determined by immunohistochemical staining, was present in 5 of the 23 tumor tissues, whereas p53 codon 249 mutations were not observed in the 5 cases in which tissue was available for study. AFB1 tumor-DNA adducts were present in 3 of 19 tumor tissues, and in 1 of these 3 samples p53 protein was also detected. Sera from only 5 of the patients were tested for AFB1-lysine adducts, and all were positive. In these five patients, neither p53 protein nor a mutation on codon 249 was detected. The demonstration that AFB1-DNA and -lysine adducts are present in HCC patients in the United States is intriguing but requires further substantiation because of the small number of subjects in this pilot study. To elucidate the pathogenetic significance of these findings, further investigation, including studies in larger patient cohorts and properly selected controls, is warranted.     

黄曲霉毒素B1诱导性大鼠肝癌超微结构观察及N-ras表达变化

目的探讨黄曲霉毒素B1(AFB1)诱导性大鼠肝癌模型超微病理特征及N-rasmRNA表达变化规律。方法 40只Wistar大鼠分为正常对照组(12只)和诱癌组(28只)用AFB1(400μg/kg)间断腹腔注射雄性Wistar大鼠制作肝癌模型,电镜观察大鼠肝组织超微结构。应用RT-PCR技术检测对照组大鼠肝组织,损伤病变、早期癌变和癌变肝组织中N-ras mRNA表达水平。结果本组大鼠肝癌模型中,肝细胞呈变性损伤,异型性到癌变;线粒体由增生肿胀到枯竭、空泡变;糖原颗粒呈逐渐减少等特征性变化。观察到典型肝细胞吞噬细胞现象。N-rasmRNA在早期癌变组织、癌变组织中表达水平均显著高于对照组大鼠肝组织和损伤病变肝组织(F=5.47,P=0.019;后者F=6.98,P=0.006)。结论 AFB1诱导性大鼠肝细胞出现变性、异型性及癌细胞渐变的超微结构特征,N-ras异常表达参与大鼠肝细胞癌变机制。     

Carnitine alters binding of aflatoxin to DNA and proteins in rat hepatocytes and cell-free systems.

The objective of this study was to determine effects of L-carnitine on aflatoxin B(1) (AFB(1))-DNA adduct formation in isolated rat hepatocytes, its dose response, specificity and mode of action. All experiments were conducted in either freshly isolated rat hepatocytes or cell-free systems. There was negative linear correlation between the dosage of carnitine and formation of [(3)H]AFB(1)-DNA adducts in the hepatocytes; however, the partitioning of AFB(1) into cellular compartments was not affected by carnitine. The attenuating effect of carnitine on AFB(1)-DNA adduct formation was also present in a cell-free system, but there was lack of specificity because acetylcarnitine and gamma-aminobutyric acid (GABA) were equally effective. Carnitine appears to interfere with bioactivation of AFB(1) and binding of AFB(1)-epoxide to DNA. On the contrary, carnitine enhanced the binding of AFB(1) and its epoxide to microsomal proteins, plasma proteins and bovine serum albumin. These results indicate that carnitine diverts AFB(1)-epoxide away from DNA by promoting binding to proteins. We conclude that modulation of AFB(1) binding to proteins and DNA by carnitine alters the carcinogenic and hepatotoxic potential of AFB(1) and poses concerns about the human AFB(1)-exposure data based on the AFB(1)-albumin adduct concentrations as a biomarker.     

P53 mutations in hepatocellular carcinoma patients in Egypt

The p53 gene plays a major role in hepatocellular carcinoma (HCC). Acquired mutations may provide clues to etiology, as some carcinogenic agents are associated with specific genetic changes in p53. Our aim was to analyze the spectrum of p53 mutations in tumor tissues from subjects with HCC in Egypt, where there is a rising incidence of HCC due to hepatitis C virus (HCV). We collected tumor tissues from 41 subjects with HCC diagnosed at the National Cancer Institute of Cairo University during 2000-2003. Sequence mutations were analyzed by the Affymetrix GeneChip technique. HCV RNA was detected in the sera of 37 subjects (90%). Only one patient had a current HBV infection. A total of 17 of the 41 subjects (41%) had p53 mutations. Thirteen of these were in exon 7, of which 10 were in codon 249, but only 8 of the 10 were the R249S mutation, previously reported to be associated with aflatoxin exposure. The other three exon 7 mutations were found in codons 232, 242 and 248. A total of three mutations were detected in exon 5 codons 133, 144 and 176. One mutation was detected in exon 8 codon 275. Unlike previous studies, this population is characterized by a high prevalence of chronic HCV infection. The presence of the R249S mutation in exon 7 may indicate that these subjects with HCC have been exposed to aflatoxin (AFB1), and further investigation is in progress to measure AFB1-albumin adducts in the sera of these subjects.     

人体血清中黄曲霉毒素-白蛋白加合物的测定及应用

黄曲霉毒素B1 (AFB1 )是人类原发性肝癌 (HCC)的主要病因之一 ,发展和应用AFB1 及其体内分子生物标记物敏感、特异的检测方法对肝癌高危人群的筛检具有重要意义。人体血清中黄曲霉毒素 白蛋白加合物 (AFB ALB)的测定已应用于人体黄曲霉毒素暴露水平与肝癌的研究 ,本研究旨在建立敏感特异的AFB ALB的测定方法。该方法选择使用Microcon 5 0微型浓缩器使白蛋白快速分离 ,改变了用沉淀和其他分离白蛋白的方法 ,同时由于在同一装置内加入蛋白分解酶消化 ,从而减少了转移操作步骤 ,增加了白蛋白的回收率 ,对消化样品采用竞争性放射免疫测定 (RIA)法进行AFB ALB的测定 ,提高了测定的敏感性及特异性。应用改进的方法对我国江苏启东和广西扶绥两肝癌高发区居民的血样进行了测定 ,表明该地区人群黄曲霉毒素暴露较普遍 ,血清AFB ALB阳性率高。     

Protective effect of soybean saponins and major antioxidants against aflatoxin B1-induced mutagenicity and DNA-adduct formation

Saponins from various plant sources have been suggested as possible anticarcinogens. Major dietary sources of saponins include legumes such as soybeans. This study was performed to determine the effect of soybean saponins on aflatoxin B(1)(AFB(1))-induced mutagenicity and AFB(1)-DNA adduct formation using Salmonella typhimurium and human liver hepatoma (HepG2) cells, respectively. Major antioxidants including L-ascorbic acid, alpha-tocopherol, all-trans-retinol, and butylated hydroxytoluene (BHT), previously reported to possess antimutagenic activity, were used as test materials to evaluate the relative effectiveness of saponins. Results indicated antimutagenicity was in the order of BHT > saponins > alpha-tocopherol > L-ascorbic acid. Soybean saponins exerted a significant effect, inhibiting the mutagenicity of AFB(1) by 52%, 64%, and 81% at concentrations of 600, 900, and 1,200 microg per plate, respectively. The amount of tritiated AFB(1) metabolites-DNA adducts formed in HepG2 cells was significantly reduced when cells were preincubated with 10 or 30 microg/ml of test materials. Soybean saponins inhibited AFB(1)-DNA adduct formation by 50.1% at a concentration of 30 microg/ml, whereas L-ascorbic acid and BHT reduced adduct formation by 38.4% and 32.6%, respectively, at the same concentrations. These results indicate that soybean saponins possess not only a significant antimutagenic activity but a strong inhibitory action against carcinogen-induced DNA damages. Soybean saponins possibly block the initiation stage of carcinogenesis, and further studies are required to elucidate the mechanisms of action.     

CD 34 expression in chronic and neoplastic liver diseases

BACKGROUND: Capillarisation of hepatic sinusoids is a well recognized phenomen occurring in long standing liver disease, in hepatic cirrhosis as well as in hepatocellular carcinoma. To study immunohistochemically the expression and distribution of CD34 in chronic liver disease and hepatocellular carcinoma in order to evaluate the possible diagnostic implication of this marker. METHODS: Sixty-five samples of liver tissue showing normal liver, different degrees of chronic inflammation, cirrhosis and histological features of hepatocellular adenoma and carcinoma (HCC) were included in the study. The specimens were fixed in formalin and embedded in paraffin and an immunohistochemical investigation was performed by the standard avidin-biotin-peroxidase complex method with CD34. RESULTS: The sinusoids of normal liver showed no immunoreactivity. The sinusoids of liver affected by different degrees of chronic active hepatitis showed no or focal immunostaining for CD34; an increased immunoreactivity was observed in the periportal sinusoids of the cirrhotic nodules whereas diffuse and strong staining was observed in the overall HCC as well as in the hepatocellular adenoma tested. CONCLUSIONS: In HCC, immunoreactivity for CD34 represents an effective method to evaluate angiogenesis and to distinguish well-differentiated HCC from non-neoplastic liver. Its role in clinical stage and prognostic evaluation needs further investigation.     

Effects of capsaicin on rat liver S9-mediated metabolism and DNA binding of aflatoxin

At concentrations of 25, 50, and 100 microM, capsaicin, which is the major component in various aspects of Capsicum hot peppers, decreased the binding of aflatoxin (AFB1) to calf thymus DNA by 19%, 44%, and 71%, respectively, in incubations with rat liver S9. At concentrations of 50 and 100 microM, capsaicin decreased the formation of AFB-DNA adducts (AFB1-N7-Gua) by 53% and 75% as determined by high-pressure liquid chromatography (HPLC). HPLC analysis of organo-soluble fractions showed that these effects correlated with a concentration-dependent decrease in S9-mediated metabolism of AFB1 by capsaicin. Capsaicin also altered the formation of water-soluble conjugates of AFB1. This was indicated by a decrease in radioactivity in water-soluble fractions and in glutathione conjugates of AFB1 analyzed by HPLC. These results suggest that capsaicin inhibited the biotransformation of AFB1 by modifying Phase I hepatic enzyme activity.     

Associations of plasma aflatoxin B1-albumin adduct level with plasma selenium level and genetic polymorphisms of glutathione S-transferase M1 and T1

Mortality from hepatocellular carcinoma (HCC) is extraordinarily high in Matzu, an island off the coast of Southeastern China. To investigate factors associated with plasma aflatoxin B1 (AFB1)-albumin adduct level, we studied 304 healthy adult residents from Matzu. AFB1-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen status by enzyme immunoassay, genotypes of glutathione S-transferase (GST) M1 and T1 by polymerase chain reaction, plasma selenium by atomic absorption spectrometry, and plasma retinol, alpha-tocopherol, alpha-carotene, and beta-carotene levels by high-performance liquid chromatography. Men had higher AFB1-albumin adduct levels than women. GSTM1-nonnull and GSTT1-null genotypes and low plasma selenium level were significantly associated with an increased level of AFB1-albumin adducts among men, whereas age was significantly correlated with adduct level among women. High intake of fermented beans was associated with an increased adduct level among men and women. The inverse associations between plasma selenium level and AFB1-albumin adducts were statistically significant among those with null genotypes of GSTM1 and GSTT1, but not among the nonnull genotypes. This study provides insight into the dietary and genetic factors influencing AFB1-albumin adduct formation in an isolated population with high liver cancer mortality.     

Is there a role for carbohydrate restriction in the treatment and prevention of cancer?

Background

Aflatoxin B1 (AFB1) is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE) on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA) level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver.

Methods

Adult, healthy balbC (20-25 g) male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks.

Results

Our results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i) a total reduction of AFB1 induced oxidative damage markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii) restriction of the effect of AFB1 by differential modulation of the expression of p53 which decreased as well as its associated genes such as bax and bcl2.

Conclusion

We concluded that CCE might have a hepatoprotective effect against aflatoxicosis in mice, probably acting by promoting the antioxidant defence systems.     

Carcinogenic effects of aflatoxin B1 among wheat handlers

Background:

Epidemiological studies have demonstrated that serum aflatoxin B1 (AFB1) is a hepatocarcinogenic mycotoxin and contributor to the high rate of hepatocellular carcinoma (HCC). The prevalence of liver cancer in Egypt is particularly worrisome. In a registry-based analysis of occupational risk for HCC, significant excesses were observed especially for grain mill workers.

Objective:

The aim of this study was to assess the hepatic carcinogenicity of AFB1 in wheat handlers.

Methods:

Serum AFB1/albumin (AFB1/Alb), alpha-fetoprotein (AFP), alpha-l-fucosidase (AFU), and arginase were estimated in exposed wheat handlers including millers and bakers. The control group was composed of non-occupationally exposed workers.

Results:

AFB1/Alb and AFU were significantly higher among workers employed as bakers compared to mill workers and controls. Mill workers had higher levels of AFB1/Alb than the controls. AFB1/Alb, AFP, and AFU were all significantly higher and arginase was significantly lower among HCC cases compared to the other groups. There was a significant correlation between AFU and AFB1/Alb in bakers and between AFP and AFB1/Alb in HCC cases. Arginase was inversely correlated with AFB1/Alb in HCC cases. AFB1/Alb was significantly correlated with the duration of exposure in bakers.

Conclusion:

Wheat handlers exposed to Aspergillus flavus have a high risk of elevated serum AFB1/Alb levels and AFU.     

Exposure to organochlorine pesticides is independent risk factor of hepatocellular carcinoma: a case--control study

Primary hepatocellular carcinoma (HCC) is highly prevalent in China. Although hepatitis B virus (HBV) and aflatoxin B1 (AFB1) are considered the major risk factors, among the high-risk cohorts only a small fraction develops liver cancer. Therefore, we investigated if organochlorine pesticides (OCPs) exposure contributed to HCC risk in the Xiamen population. The questionnaire database was built from 346 HCC cases and 961 healthy controls during 2007-2009. The serum levels of α-, β-, γ-, δ-HCH, p, p'-DDT, p, p'-DDE, o, p'-DDT and p, p'-DDD were measured by gas chromatography-tandem mass spectrometer and statistical analysis was done using SPSS16. Significantly, we observed p, p'-DDT, p, p'-DDE, and at first time β-HCH displayed quartile dose-dependent HCC risk trends; p, p'-DDT showed positive (i.e., synergistic) interactions with HBV, diabetes mellitus, AFB1 and polycyclic aromatic hydrocarbon (PAH) exposure, but negative (i.e., antagonistic) interaction with heavy drinking; p, p'-DDE had positive interaction with PAH but negative interaction with HBV and p, p'-DDT; and β-HCH was positively interacted with p, p'-DDT but negatively interacted with heavy drinking and diabetes. p, p'-DDT, p, p'-DDE and β-HCH were independent HCC risk factors. Because of their synergistic interactions with other factors, the high level exposure combined with common AFB1 and HBV exposure in the investigated area may greatly enhance the risk of HCC.     

肝细胞癌合并肝硬化患者癌组织、癌旁肝组织ALB

目的探讨肝细胞癌合并肝硬化患者癌组织、癌旁肝组织ALBmRNA、IGF-1mRNA、IGFBP-3mRNA的表达。方法对24例肝细胞癌合并肝硬化行手术的患者和12例因胆石症或肝血管瘤行手术的患者进行研究。用RT—PCR法检测肝组织（包括癌组织、癌旁组织）ALBmRNA、IGF-1mRNA、IGFBP-3mRNA的表达,肝组织行Ki67免疫组织化染色。结果肝细胞癌合并肝硬化患者癌组织、癌旁肝组织ALBmRNA、IGF-1mRNA、IGFBP-3mRNA表达水平明显低于正常肝组织,且癌组织ALBmRNA、IGFBP-3mR．NA表达水平明显低于癌旁肝组织,而IGF-1mRNA表达水平明显高于癌旁肝组织。肝组织Ki67指数,癌组织、癌旁肝组织明显高于正常肝组织,且癌组织明显高于癌旁肝组织。结论IGF—1和IGFBP-3的不平衡可能与肝硬化患者肝癌的发生、发展有关。     

Hepatocellular carcinoma in a non-cirrhotic liver. Two case reports and literature review

Hepatocellular carcinoma (HCC) is closely associated with cirrhosis, but it also develops, although much less frequently, in a non-cirrhotic liver. It is suspected that hepatocellular carcinoma has a different etiology when associated and not associated with chronic liver disease. We report two cases of patients with hepatocellular carcinoma that developed in a non-cirrhotic liver. In the first case we describe an incidental liver nodular lesion containing multiple foci of HCC including pseudogland or trabecular formation and areas of sclerosis. The non-cancerous parenchyma of the liver was histologically unremarkable except for mild fatty changes of hepatocytes and minimal dysplasia. The second case describes a combined hepatocellular carcinoma and cholangiocellular carcinoma (CCC) (mixed carcinoma) in a patient who was serologically negative for both hepatitis B and C viruses. The adjacent liver parenchyma showed mild piecemeal necrosis and mild lobular activity compatible with chronic viral hepatitis, but cirrhosis was not established. This case appears to indicate that mixed type carcinoma can develop in a non-cirrhotic liver, with CCC being far more dominant than HCC; such a finding is extremely unusual, based on previously published reports.     

人类膜联蛋白Ⅳ在肝细胞性肝癌中的表达及其意义

目的 研究人类膜联蛋白Ⅳ(ANXA4)在不同表型肝癌组织中的表达情况,探讨其临床病理意义.方法 先应用半定量RT-PCR技术验证ANXA4在不同类型肝组织中的基因表达,再应用免疫组化方法检测其在正常肝组织、乙型病毒性肝炎(乙肝)后肝硬化组织和不同表型肝癌组织标本中的表达,探讨其表达与临床病理资料之间的联系及其意义.结果 半定量RT-PCR扩增出长为300 bp的ANXA4片段,相对于520 bp的内参照β-actin片段计算,灰度的平均比值在正常肝组织、乙肝后肝硬化组织、肝癌组织中分别为0.3410±0.0161、0.8700±0.0341和0.9323±0.0142,两两比较差异均有统计学意义.免疫组化研究表明:ANXA4在正常肝组织中总阳性率为24.0%,在乙肝后肝硬化组织中总阳性率为28.0%;在肝癌组织中总阳性率为49.4%,相应癌旁组织中总阳性率为62.4%,其中小肝癌组织中总阳性率为53.8%,大肝癌组织中总阳性率为64.5%,多发癌组织中总阳性率为28.6%,相应癌旁组织中总阳性率分别为53.8%、64.5%、67.9%.统计学分析表明:随着肝细胞的恶性转化并进展,ANXA4呈逐渐上调趋势,但当肿瘤出现侵袭性转移时反而下调.与临床病理指标的相关性研究表明ANXA4与肝癌进展及侵袭相关.结论 从正常肝→肝硬化→肝癌组织,ANXA4的mRNA表达水平逐渐上调,与组织学蛋白表达水平变化相一致,提示与肝癌发生有关;ANXA4在肝癌组织中的表达明显失调,其变化可能与肝癌进展及侵袭相关.     

Exposure to organochlorine pesticides is an independent risk factor of hepatocellular carcinoma: A case-control study

Primary hepatocellular carcinoma (HCC) is highly prevalent in China. Although hepatitis B virus (HBV) and aflatoxin B1 (AFB1) are considered the major risk factors, among the high-risk cohorts only a small fraction develops liver cancer. Therefore, we investigated whether organochlorine pesticide exposure contributed to HCC risk in the Xiamen population. The questionnaire database was built from 346 HCC cases and 961 healthy controls during 2007-2009. The serum levels of α-, β-, γ-, δ-HCH, 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (p,p'-DDT), (1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE), 1,1,1-trichloro-2,2-bis (o-chlorophenyl) ethane and 1,1-dichloro-2,2-bis (p-chlorophenyl) ethane were measured by gas chromatography-tandem mass spectrometer, and statistical analysis was done using SPSS16. Significantly, we observed p,p'-DDT and p,p'-DDE, and at the first time β-HCH displayed quartile dose-dependent HCC risk trends; p,p'-DDT showed positive (i.e., synergistic) interactions with HBV, diabetes mellitus, AFB1 and polyaromatic hydrocarbon (PAH) exposure, but negative (i.e., antagonistic) interaction with heavy drinking; p,p'-DDE had positive interaction with PAH but negative interaction with HBV and p,p'-DDT; and β-HCH positively interacted with p,p'-DDT but negatively interacted with heavy drinking and diabetes. p,p'-DDT, p,p'-DDE and β-HCH were independent HCC risk factors. Because of their synergistic interactions with other factors, the high-level exposure combined with common AFB1 and HBV exposure in the investigated area may greatly enhance the risk of HCC.     

镰刀菌毒素与黄曲霉毒素的联合毒性研究--AFB1和DON的RDS实验

为了解黄曲霉毒素（ＡＦＢ１）与镰刀菌毒素的脱氧雪腐镰刀菌烯醇（ＤＯＮ）对ＤＮＡ损伤修复的影响,用化学物质诱导的细胞增殖的变化实验,（ｒｅｐｌｉｃａｔｉｖｅ ＤＮＡ ｓｙｎｔｈｅｓｉｓ,ＲＤＳ）实验进行研究。结果表明：ＡＦＢ１和ＤＯＮ均可诱导细胞分化的Ｓ期ＤＡＮ的合成,并且二者间存在交互作用。结果提示：ＡＦＢ１与ＤＯＮ在肿瘤的发生中既以遗传毒性物质的形式发挥作用,又以非遗传毒性物质的形式共同发挥作用     

Increased risk of hepatocellular carcinoma and liver cirrhosis in vinyl chloride workers: synergistic effect of occupational exposure with alcohol intake

Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) are not well-established vinyl chloride monomer (VCM)-induced diseases. Our aim was to appraise the role of VCM, alcohol intake, and viral hepatitis infection, and their interactions, in the etiology of HCC and LC. Thirteen cases of HCC and 40 cases of LC were separately compared with 139 referents without chronic liver diseases or cancer in a case-referent study nested in a cohort of 1,658 VCM workers. The odds ratios (ORs) and the 95% confidence intervals (CIs) were estimated by common methods and by fitting models of logistic regression. We used Rothman's synergy index (S) to evaluate interactions. By holding the confounding factors constant at logistic regression analysis, each extra increase of 1,000 ppm times years of VCM cumulative exposure was found to increase the risk of HCC by 71% (OR = 1.71; 95% CI, 1.28-2.44) and the risk of LC by 37% (OR = 1.37; 95% CI, 1.13-1.69). The joint effect of VCM exposure above 2,500 ppm times years and alcohol intake above 60 g/day resulted in ORs of 409 (95% CI, 19.6-8,553) for HCC and 752 (95% CI, 55.3-10,248) for LC; both S indexes suggested a synergistic effect. The joint effect of VCM exposure above 2,500 ppm times years and viral hepatitis infection was 210 (95% CI, 7.13-6,203) for HCC and 80.5 (95% CI, 3.67-1,763) for LC; both S indexes suggested an additive effect. In conclusion, according to our findings, VCM exposure appears to be an independent risk factor for HCC and LC interacting synergistically with alcohol consumption and additively with viral hepatitis infection.     

Organosulfur compounds of garlic modulate mutagenesis, metabolism, and DNA binding of aflatoxin B1

The effects of two organosulfur compounds of garlic (ajoene and diallyl sulfide) and a crude garlic extract on aflatoxin B1 (AFB1)-induced mutagenesis were determined using rat liver 9,000 g supernatant (S-9) as the activation system and Salmonella typhimurium TA-100 as the tester strain. The effects of these compounds on AFB1 binding to calf thymus DNA were also measured. Metabolites of AFB1 were isolated and analyzed by reverse-phase high-performance liquid chromatography. All these compounds inhibited S-9-dependent mutagenesis induced by AFB1. They also inhibited AFB1 binding to DNA. A significant decrease in organo-soluble metabolites of AFB1 was observed with ajoene and garlic extract. An increase of glucuronide and glutathione conjugates was obtained with garlic extract. The results indicate that garlic compounds tested in this study are antimutagenic and, potentially, anticarcinogenic.     

厦门市不同吸烟类型与其他危险因素致肝癌效应修饰作用

目的 评价不同类型吸烟暴露的单独效应,并分析吸烟在肝癌发病中的效应修饰作用.方法 采用病例对照研究方法,对345例肝癌病例和961例健康对照进行危险因素调查,采集血液标本进行HBsAg、抗-HCV和黄曲霉毒素(AFB1)白蛋白加合物等含量的检测,针对潜在的危险因素应用多元logistic回归分析评价调整的危险比(AOR)和95%CI.结果 女性被动吸烟暴露与肝癌有关联(AOR=2.35,95%CI:1.19～4.07);男性规律的吸烟与肝癌有关联(AOR=2.27,95%CI:1.14～3.31).在男性,吸烟与慢性乙肝病毒感染有正相关交互作用,交互效应超额相对危险比(RERI)为98.70,归因交互效应百分比(AP)为81.0%(u=2.11,P=0.02);在女性,吸烟与血清AFB1白蛋白加合物浓度有正相关交互作用,交互效应RERI为2.69,归因交互效应AP为50.0%(u=2.60,P=0.01).结论 吸烟与肝癌的关联性有性别差异,尤其是在慢性病毒感染和具有较高浓度的AFB1白蛋白加合物浓度的人群中应控制吸烟.