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.     

Determinants of aflatoxin levels in Ghanaians: sociodemographic factors, knowledge of aflatoxin and food handling and consumption practices

Aflatoxins are among the most potent of carcinogens found in staple foods such as groundnuts, maize and other oil seeds. This study was conducted to measure the levels of aflatoxin B(1) (AFB(1)) albumin adducts in blood and aflatoxin M(1) (AFM(1)) metabolite in urine of people in a heavy peanut and maize consuming region of Ghana and to examine the association between aflatoxin levels and several socio-demographic factors and food handling and consumption practices. A cross-sectional study was conducted in four villages in the Ejura Sekyedumase district of Ghana. A socio-demographic survey was administered to 162 participants. Blood samples were collected from 140 and urine samples from 91 of the participants and AFB(1) albumin-adduct levels in blood and AFM(1) levels in urine were measured. High AFB(1) albumin-adduct levels were found in the plasma (mean+/-SD=0.89+/-0.46pmol/mg albumin; range=0.12-3.00pmol/mg; median=0.80pmol/mg) and high AFM(1) levels in the urine (mean+/-SD=1,800.14+/-2602.01pg/mg creatinine; range=non-detectable to 11,562.36pg/mg; median=472.67pg/mg) of most of the participants. There was a statistically significant correlation (r=0.35; p=0.007) between AFB(1)-albumin adduct levels in plasma and AFM(1) levels in urine. Several socio-demographic factors, namely, educational level, ethnic group, the village in which participants lived, number of individuals in the household, and number of children in the household attending secondary school, were found to be significantly associated with AFB(1) albumin-adduct levels by bivariate analysis. By multivariate analyses, ethnic group (p=0.04), the village in which participants live (p=0.02), and the number of individuals in the household (p=0.01), were significant predictors of high AFB(1) albumin-adducts. These findings indicate strongly that there is need for specifically targeted post-harvest and food handling and preparation interventions designed to reduce aflatoxin exposure among the different ethnic groups in this region of Ghana.     

Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress

Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins.     

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.     

Associations of serum aflatoxin B1-lysine adduct level with socio-demographic factors and aflatoxins intake from nuts and related nut products in Malaysia

Aflatoxins are one of the major risk factors in the multi-factorial etiology of human hepatocellular carcinoma. Therefore, the information on aflatoxins exposure is very important in the intervention planning in order to reduce the dietary intake of aflatoxins, especially among the children. This study investigated the relationship between aflatoxin B(1) (AFB(1)) lysine adduct levers in serum and socio-demographic factors and dietary intake of aflatoxins from nuts and nut products in Penang, Malaysia. A cross-sectional field study was conducted in five districts of Penang. A survey on socio-demographic characteristics was administered to 364 healthy adults from the three main ethnic groups (Malay, Chinese and Indian). A total of 170 blood samples were successfully collected and tested for the level of AFB(1)-lysine adduct. 97% of the samples contained AFB(1)-lysine adduct above the detection limit of 0.4 pg/mg albumin and ranged from 0.20 to 23.16 pg/mg albumin (mean±standard deviation=7.67±4.54 pg/mg albumin; median=7.12 pg/mg albumin). There was no significant association between AFB(1)-lysine adduct levels with gender, district, education level, household number and occupation when these socio-demographic characteristics were examined according to high or low levels of AFB(1)-lysine. However, participants in the age group of 31-50 years were 3.08 times more likely to have high AFB(1) levels compared to those aged between 18 and 30 years (P=0.026). Significant difference (P=0.000) was found among different ethnic groups. Chinese and Indian participants were 3.05 and 2.35 times more likely to have high AFB(1) levels than Malay. The result of AFB(1)-lysine adduct suggested that Penang adult population is likely to be exposed to AFB(1) but at a level of less than that needed to cause direct acute illness or death.     

Benzo(a)pyrene-blood protein adducts in wild woodchucks used as biological sentinels of environmental polycyclic aromatic hydrocarbons contamination

Levels of benzo(a)pyrene-diolepoxide (BaPDE)-albumin and BaPDE-hemoglobin adducts in wild woodchucks (Marmota monax) have been measured to evaluate the potential usefulness of these parameters in the assessment of environmental contamination by polycyclic aromatic hydrocarbons (PAHs). Blood was obtained from nine woodchucks living near an aluminum electrolysis plant, contaminated area (Saguenay region, Québec, Canada), and from eight living in a control area (Saint-Roch-des-Aulnaies, Québec, Canada). Blood samples were collected and plasma separated from red blood cells by centrifugation on site. Isolation of albumin (Alb) and hemoglobin (Hb) was performed in our laboratory and each protein fraction was subjected to mild acid hydrolysis yielding free benzo(a)pyrene (BaP) tetrol from the adducts. The analysis was performed by high performance liquid chromatography (HPLC) using fluorescence detection. For the control and contaminated areas geometric mean (interval) Alb adduct levels were 7.6 (0.8–29.3) and 69.6 (10.0–1,103) pmol tetrol/g protein (p<0.01) while the corresponding figures for Hb adduct levels were 0.40 (0.01–2.72) and 1.18 (0.02–12.8) pmol/g protein (p>0.01). Alb but not Hb adduct levels were associated with the measured concentration of BaP in the vegetation samples collected on the site where each animal was found. This is compatible with the short half-life of Alb adducts and with the instantaneous image provided by BaP measurements in the collected vegetation samples. BaPDE-blood protein adducts measured in wild animals appear to be good biomarkers of environmental contamination by PAHs.     

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.     

Effects of dietary selenium and vitamin E on covalent binding of aflatoxin to chick liver cell macromolecules

Day-old single comb white Leghorn chicks of both sexes maternally depleted in selenium (Se) and vitamin E (VE) were fed a low Se and VE-free semipurified basal diet or that diet supplemented with graded levels of Se (0.2 - 20.0 ppm as Na2SeO3) of VE (100 IU/g as all-rac-alpha-tocopheryl acetate), or both. At 14 days of age, chicks were given 1 mg/kg [3H] aflatoxin B1 (AFB1) i.p. and killed either 2 or 24 hours later. Covalent binding of AFB1 to liver DNA and RNA in chicks fed the basal diet was significantly greater than in chicks supplemented with Se or VE, or both. Phenobarbital treatment prior to administration of AFB1 decreased adduct formation in most groups, and abolished differences in adduct formation due to diet. These results suggest that combined Se-VE deficiency enhances activation or inhibits detoxification of AFB1 in vivo.     

Determination of haemoglobin adducts of acrylamide and glycidamide in smoking and non-smoking persons of the general population

Acrylamide (AA) is a food-borne toxicant suspected to be carcinogenic to humans. It is formed in the heating process of starch-containing food. Currently, there is a great discussion about the possible human health risks connected with the dietary uptake of acrylamide. Haemoglobin adducts of acrylamide and its oxidative metabolite glycidamide are both markers of biochemical effect. However, because glycidamide has a higher carcinogenic potency than acrylamide itself, the glycidamide adduct might mirror the genotoxicity better than acrylamide adducts. In order to gain more information about the human metabolism of acrylamide, we investigated a small group of persons for the effective internal doses of acrylamide and glycidamide using haemoglobin adducts as parameters of biochemical effect.

The collective was subdivided into non-smokers (n=13) and smokers (n=16) by determining the smoking-specific acrylonitrile haemoglobin adduct (N-cyanoethylvaline, CEV). The mean values for the adducts of acrylamide (N-2-carbamoylethylvaline, AAVal) and glycidamide (N-(R,S)-2-hydroxy-2-carbamoylethylvaline, GAVal) in nonsmokers was 19 pmol/g globin AAVal (range 7 – 31 pmol/g globin) and 17 pmol/g globin GAVal (range 9 – 23 pmol/g globin). For smokers mean levels of AAVal were 80 pmol/g globin (range: 25 – 199 pmol/g globin) and those of GAVal were 53 pmol/g globin (range: 22 – 119 pmol/g globin). Metabolism to glycidamide turned out to be significantly more effective in non-smokers than in the higher exposed smokers. Compared with studies in rats, the metabolic conversion of acrylamide to glycidamide as measured by haemoglobin adducts seems to occur to a similar extent in humans as in rats. Risk estimations on acrylamide based on experimental data obtained in rats obviously did not overestimate the cancer risk for the general population. Furthermore, our results might indicate that the dose-response curve for acrylamide is not linear. This would be in line with the results of animal experiments on rodents.     

Trans-placental exposure of neonates to acrylamide—a pilot study

Objectives Acrylamide (AA) (CAS No 79-06-1) has most recently been identified as a food-borne toxicant generated during the heating process of starch-containing foods. It was the aim of the present study to investigate the trans-placental exposure of newborn infants to this possible human carcinogen by analysis of the specific haemoglobin adduct of AA (N-2-carbamoylethylvaline, AAV) in the blood of mothers and the corresponding umbilical cord blood of neonates as a parameter of biochemical effects.Methods We investigated the blood of 11 women advanced in pregnancy (one smoker, ten non-smokers) and the corresponding umbilical cord blood of neonates for the N-terminal haemoglobin adducts of AA (AAV) and the smoking-specific adduct of acrylonitrile (CAS No 107-13-1) (N-cyanoethylvaline, CEV). The limit of detection (LOD) was 5 pmol/g globin for AAV and 4 pmol/g globin for CEV.Results AAV could be determined in all blood samples of the mothers (median 21 pmol/g globin, range 18–104 pmol/g globin) as well as in the umbilical cord blood of neonates (median 10 pmol/g globin, range 6–43 pmol/g globin). The highest values were detected in the blood of the smoking mother and her child. CEV was detected only in the blood of the smoking mother (185 pmol/g globin) and the corresponding umbilical cord blood (69 pmol/g globin).Discussion AAV adduct levels in non-smoking mothers and neonates showed a good correlation (r=0.859). The concentration of AA adducts in the blood of neonates is approximately 50% of the adduct level found in the blood of the mother. In view of the shorter life span of neonatal erythrocytes and the lower body weight of newborn infants, the relative internal dose of AA in neonates (in microgrammes per kilogramme body weight) must be assumed to be at least equal to that of the mother. Because of the high cell-replication rates during foetal development, trans-placental exposure of neonates to AA might raise concerns. Neonates of smoking mothers take up much higher doses of AA than those of non-smoking mothers.     

Benzo(a)pyrene-albumin adducts in humans exposed to polycyclic aromatic hydrocarbons in an industrial area of Poland.

OBJECTIVES: The interaction of benzo(a)pyrene with serum albumin was measured in an attempt to identify the actual exposure and to evaluate albumin adduct measurements as biomarkers for exposure monitoring. METHODS: Benzo(a)pyrene-diol-epoxide (BPDE)-albumin adducts were measured by competitive enzyme linked immunosorbent assay (ELISA) in plasma of coke oven plant workers from three plants and from people living in a highly industrialised area of Silesia in Poland. Due to the high air concentrations of polycyclic aromatic hydrocarbons (PAHs) in this area, a control group was selected from a rural non-industrialised area in Poland. Breathing zone air measurements of PAHs were collected from some of the participants. RESULTS: Coke oven plant workers and non-occupationally exposed people had similar concentrations of albumin adducts whereas the rural controls were significantly lower (2.74 fmol adducts/microgram albumin (SEM 0.124)). The mean concentration of BPDE-albumin adduct in plasma of both the occupational and the environmental groups were significantly higher in the summer samples (4.34 fmol adducts/microgram albumin (SEM 0.335) and 4.55 fmol adducts/microgram albumin (SEM 0.296), respectively) than in the winter samples (3.06 fmol adducts/microgram albumin (SEM 0.187) and 3.04 fmol adducts/microgram albumin (SEM 0.184), respectively) even though the air measurements showed higher concentrations of PAHs in the winter. The statistical analysis did not show any effects of air exposures on concentrations of BPDE-albumin adduct. CONCLUSIONS: A multiple regression analysis of the measured concentrations of BPDE-albumin adducts for all the groups, during both seasons, indicates that occupational exposures do not contribute significantly to the formation of adducts. In general, the concentrations of albumin adducts found vary within relatively small limits for the two seasons and between the various groups of participants. No extreme differences were found.     

Effects of dietary selenium and vitamin E on hepatic mixed-function oxidase activities and in vivo covalent binding of aflatoxin B1 in rats

Male weanling fischer-344 rats were fed a selenium (Se)-vitamin E (VE) deficient Torula yeast basal diet or that diet supplemented with a graded levels of SE (0.2-6.0 ppm as Na2SeO3) or VE (100 iu/kg as all-rac-2-tocopheryl acetate), or both, for 4 or 6 weeks. Se deficiency and excess (6.0 ppm) markedly depressed in vivo covalent binding of aflatoxin (AFB1) to macromolecules in livers of rats killed 2 hours after an i.p. dose of 1 mg/kg tritiated AFB1. VE supplementation had no effect. Prior phenobarbital (PB) treatment generally decreased adducts without changing diet-related trends. Some hepatic enzyme capabilities were also measured. Cytochrome b5 content and cytochrome c reductase activity were unaffected by diet. VE increased cytochrome P-450 content, ethylmorphine N-demethylase and benz(alpha)pyrene hydroxylase activities; all these were unaffected by Se levels. Se deficiency and excess (but not VE deficiency) increased glucuronyl transferase. PB induction affected all diet groups and was more in agreement with MFO activity than transferase. Adduct formation was more consistently related to transferase activity than to MFO activities. The contrasting effects of SE and VE on AFB1 adducts in rats and chicks are discussed.     

苯DNA加合物的形成特征,条件和方法探讨

为进一步探讨苯ＤＮＡ加合物的形成特征，稳定地检测苯ＤＮＡ加合物，采用３２Ｐ－后标记法对染苯小鼠体内ＤＮＡ加合物的形成特征及影响因素进行了研究。结果表明：加合物种类与染苯天数有关：５００ｍｇ／ｋｇ染苯５天组外周血白细胞可检出２个ＤＮＡ加合物斑点，而７天组可检出３个主要的和至少１个微弱的加合物斑点；染苯达一定剂量后，加合物含量和种类不再增加，１０００ｍｇ／ｋｇ与５００ｍｇ／ｋｇ染苯７天组的检测结果基本相同；苯醌可能是苯形成ＤＮＡ加合物的主要代谢产物，２．５ｍｇ／ｋｇ苯醌染毒５天的小鼠白细胞中可检出３个主要的及２个微弱的加合物斑点，其层析特性与染苯小鼠加合物的层析性质基本一致。提示：动物染苯天数及次数、层析点样量及层析时间对加合物斑点形成均有影响。     

Plasma carotenoids, glutathione S-transferase M1 and T1 genetic polymorphisms, and risk of hepatocellular carcinoma: independent and interactive effects

This study was conducted to assess the role of carotenoid and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in the development of hepatocellular carcinoma (HCC). A total of 84 incident cases of HCC and 375 matched controls selected from a cohort of 7,342 men (4,841 chronic hepatitis B carriers and 2,501 noncarriers) who were recruited between 1988 and 1992 in Taiwan were studied. Neither GST M1/T1 polymorphisms nor plasma levels of various carotenoids were independently associated with HCC, but they modulated smoking- and/or drinking-related HCC risk. Cumulative exposure to tobacco smoke significantly increased HCC risk in a dose-dependent manner among subjects with low plasma beta-carotene levels (p for trend = 0.047) but not among those with high levels. A statistically significant effect of habitual alcohol drinking on HCC risk was observed only for those with low plasma levels of beta-carotene, alpha-carotene, or lycopene and for GST M1 null subjects. There was evidence suggesting an interaction between the GST M1/T1 genotype and certain carotenoids in HCC associated with smoking and drinking. The strongest effect of smoking and drinking was noted among GST M1 null subjects with low plasma levels of beta-carotene (smoking: adjusted odds ratio (OR) = 3.54, 95% confidence interval (CI) 1.06-11.83; drinking: OR = 8.28, 95% CI 2.40-28.61).     

Monitoring exposure to simple epoxides and alkenes through gas chromatographic determination of hemoglobin adducts

Summary A method for monitoring exposure to ethylene oxide (EO) and propylene oxide (PO) and their corresponding alkenes through the analysis of adducts to N-terminal valine in hemoglobin (Hb) using gas chromatography (GC) and electron-capture detection has been developed. The method is a further development of the so-called N-alkyl Edman method, which has thus far been carried out using gas chromatography-mass spectrometry (GC/MS). The correlation between GC and GC/MS determinations of adduct levels in human samples was found to be good. The newly developed GC method enables the determination of adducts to Hb from EO and PO down to levels of about 100 pmol/g globin. This adduct level corresponds to the expected increment from ethene in inhaled tobacco smoke in a smoker of about 10 cigarettes/day or from an average exposure to about 50 Wpb EO or 1 Wpm PO during working hours.     

Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area

Aflatoxin B1 (AFB1) is a class 1 carcinogen with an ascertained role in the development of hepatocellular carcinoma (HCC) in high exposure areas. Instead, this study aimed to assay whether chronic/intermittent, low-dose AFB1 consumption might occur in low-exposure geographical areas, ultimately accumulating in the liver and possibly contributing to liver cancer. AFB1-DNA adducts were assayed by immunostaining in liver tissues from three Italian series of twenty cirrhosis without HCC, 131 HCC, and 45 cholangiocarcinoma, and in an AFB1-induced HCC rat model. CD68, TP53 immunostaining, and TP53 RFLP analysis of R249S transversion were used to characterize cell populations displaying AFB1-DNA adducts. Twenty-five HCCs displayed AFB1-adducts both in neoplastic hepatocytes and in cells infiltrating the tumor and non-tumor tissues. Nuclear immunostaining was observed in a few cases, while most cases showed cytoplasmic immunostaining, especially in CD68-positive tumor-infiltrating cells, suggestive for phagocytosis of dead hepatocytes. Similar patterns were observed in AFB1-induced rat HCC, though with higher intensity. Cholangiocarcinoma and cirrhosis without HCC did not displayAFB1-adducts, except for one case. Despite not providing a causal relationship with HCC, these findings still suggest paying attention to detection and control measures for aflatoxins to ensure food safety in low exposure areas.     

Aromatic DNA adducts in coke-oven workers, in relation to exposure, lifestyle and genetic polymorphism of metabolic enzymes

Objective: This study investigates the effect of multiple factors, including exposure to polycyclic aromatic hydrocarbons (PAHs), lifestyle, genetic polymorphism of cytochrome P450 (CYP)1A1, glutathione transferase (GST)M1, GSTP1, N-acetyltransferase (NAT)2 and gene p53, as well as any family history of cancer, on DNA adduct levels in coke-oven workers. Methods: Sixty-five coke-oven workers employed at the largest iron-steel factory in China were recruited for the study. Personal data were collected at the interview. DNA adduct levels in total white blood cells (WBCs) were detected using ³²P-postlabeling techniques. Genetic polymorphisms were analyzed by polymerase chain reaction (PCR) methods. Results: The subjects were divided into low and high exposure groups, according to personal exposure to PAHs. The mean adduct value was 1.57 (range 0.54 to 4.35) per 10⁸ nucleotides. A tendency for increased levels of DNA adducts in the high exposure group was observed, compared with the low exposure group (P = 0.07). In the low exposure group, DNA adducts were found to be positively associated with urinary cotinine (r = 0.44, P = 0.01). The rare allele homozygotes of CYP1A1 showed significantly higher DNA adduct levels than those of other CYP1A1 genotypes. Individuals with the NAT2 wild type had significantly increased DNA adduct levels than those with other NAT2 genotypes in the high exposure group. The p53 genetic polymorphism revealed a significantly positive effect on DNA adducts formation. There was a significantly higher adduct level in the subjects with a family history of cancer than those without, in the high exposure category. Conclusions: Effects of several variables, such as smoking, genetic polymorphism of 2 CYP1A1, NAT2, and gene p53, and a family history of cancer on DNA adduct levels were found, suggesting that these variables should be considered when evaluating the genotoxic effect of occupational exposure to PAHs using WBCs DNA adducts. Received: 15 February 1999 / Accepted: 15 June 1999     

绿茶抑制大鼠体内杂环胺-DNA加合物的形成

食物中的致突变物２－氨基－１－甲基－６－苯基咪唑并「４，５－ｂ」吡啶可诱发大鼠结肠和乳腺肿瘤，而且与人类癌症特别是结肠和直肠癌的密切关系。本研究以致癌物－ＤＮＡ加合物为生物标记物，观察绿茶对ＰｈＩＰ致癌作用的预防效果及机理。     

Styrene-oxide N-terminal valine haemoglobin adducts as biomarkers of occupational exposure to styrene

Styrene is widely used in the production of various plastics, synthetic rubber and resins. Occupational exposure occurs mainly via inhalation and relatively high exposure occurs due to its use in manual application techniques. The aim of this study was to evaluate if SO-Hb adducts are a suitable biomarker for assessing occupational exposure to styrene. Seventy-five reinforced plastic workers and 77 control subjects were studied. In the selected population the main urinary styrene metabolites and the styrene oxide N-terminal valine (SO-Hb) adducts in human globin were quantified. The levels of SO-Hb adducts were significantly higher (p<0.01) in the exposed subjects (5.98 pmol/g globin) when compared with controls (2.59 pmol/g globin) and a significant difference was found in levels of SO-Hb adducts between non-smokers and smokers among the control group. From our data we conclude that SO-Hb adduct measurement is a sensitive and specific means of assessing exposure to styrene at the occupational and environmental level.