Assessment of usefulness of synchrotron radiation techniques to determine arsenic species in hair and rice grain samples.

The arseniasis in Southwest Guizhou, China has been identified as a unique case of endemic arseniasis caused by exposure to indoor combustion of high As-content coal. Present investigation targeted the microdistribution and speciation of the element arsenic in human hair and environmental samples collected in one of the hyper-endemic villages of arseniasis in the area. Analyses were performed by micro-beam X-ray fluorescence (µ-XRF) and X-ray absorption fine structure (XAFS). The total As level in hair samples of diagnosed patients was detected at almost the same level as in their asymptomatic neighbors. Concentrations in the lateral cut of hair samples were high-low-high (from surface to center). XAFS revealed the coexistence of both the As+3 and As+5 states in hair samples. However, the samples from patients displayed a tendency of higher As+3 / As+5 ratio than the asymptomatic fellow villagers. The µ-XRF mapping of rice grains shows that arsenic penetrates the endosperm, the major edible part of the grain, when rice grains were stored over the open fire of high As-content coal. Synchrotron radiation techniques are suitable to determine arsenic species concentrations in different parts of hair and rice grain samples. As arsenic penetrates the endosperm, rinsing the rice grains with water will remain largely ineffective.

Co-occurrence of arseniasis and fluorosis due to indoor combustion of high fluorine and arsenic content coal in a rural township in northwest China: epidemiological and toxicological aspects.

A large number of fluorosis and arseniasis cases appeared in a mountainous area in northwest China. The residents relied on local inferior coal ("bone coal") of high fluorine and arsenic content for domestic heating and cooking. For deep-inside information about this rare case of co-endemia of fluorosis and arseniasis in the population in this special exposure scenario, a field investigation in one of the hyperendemic townships was conducted. The resident population registered (n = 27,713) was enrolled in the investigation. All cases were diagnosed and assigned to three symptom severity groups, that is severe, medium, and mild according to Chinese National Standard Criteria GB 16396-96 and to the technical guideline WS/T208-01 or WS/T211-01 issued by the Chinese Ministry of Health. Gender difference was analyzed by standardized incidence ratio. Age trend and severity trend were tested by χ(2) analysis. Fluorosis was diagnosed in 56.7% of the residents. Over 95% of the diagnosed arseniasis cases were simultaneously diagnosed with fluorosis symptoms. Combined fluorosis-arseniasis represented 11.9% of the total fluorosis cases and 6.7% of the local population. No gender-related differences in the prevalence of skeletal, dental, or dermal symptoms inside all severity groups were detected. Symptom severity increased with age. The high frequency of superposition of arseniasis with fluorosis might be due to the fact that the local resident population has been exposed to very high levels of fluorine and arsenic via the same exposure route.

N-Acetyltransferase 2 genotype, exfoliated urothelial cells and benzidine exposure.

Most studies report an association of the slow N-acetyltransferase 2 (NAT2) status with elevated bladder cancer risk. In this study, NAT2 genotypes and the decades-long records of Papanicolaou's grading of exfoliated urothelial cells in a former benzidine-exposed cohort of the Shanghai dyestuff industry (29 bladder cancer patients; 307 non-cancer cohort members, some of them presenting different grades of pre-malignant alterations of exfoliated urothelial cells) were investigated. The cohort members had been enrolled in regular medical surveillance since mid-1980s. No overall increase of slow NAT2 genotypes in the former benzidine-exposed bladder cancer patients was found, compared with non-diseased members of the same cohort. A lower presentation of the homozygous wild genotype NAT2 4/4 was observed in bladder cancer patients, compared with non-diseased members with averaged Papanicolaou's grading (APG)3 II (OR=0.31, 95 percent CI 0.10-0.96, p=0.034) or with APG less than II (OR=0.36,95 percent CI 0.12-1.10, p=0.063). Nevertheless, neither a protective influence of rapid NAT2 genotypes on bladder cancer risk nor on pre-malignant cytological alterations could be confirmed by the present data.

The occurrence of polycyclic aromatic hydrocarbons in Peking duck: Relevance to food safety assessment.

Peking duck is one of the most well-known Chinese dishes. GC-MS analysis revealed that, either benzo(a)pyrene alone, or the total amount of major PAHs with carcinogenic potential for humans, reached levels of 8.7 and 54.7µg/kg, respectively. These levels greatly exceeded those found in grilled poultry in European countries. However, the intake of benzo(a)pyrene from a Peking duck meal (about 0.65µg) was not higher than that from the daily intake (for residents in the same area) from vegetables alone (about 2µg/day). Since Peking duck is still not a plebeian meat in this country, people would not consume it very often.

Factors impacting on the excess arseniasis prevalence due to indoor combustion of high arsenic coal in a hyperendemic village.

BACKGROUND: A few villages in Southwest Guizhou, China represented a unique case of arseniasis due to indoor combustion of high arsenic-content coal. The present study is aimed to analyze the contribution of possible factors or of their combination to excess prevalence of arseniasis in the exposed population. METHODS: An epidemiological investigation was conducted in all the members of three large ethnic, patrilineal clans in one of the hyperendemic villages (702 residents in 178 families, including 408 Han and 294 Hmong) where farmers of different ethnic origin have been living together in the same village for generations. A multilevel model logistic regression analysis was performed. RESULTS: The arseniasis prevalence was found to associate with the duration of As indoor exposure (years of high As coal burning and of poorly ventilated traditional stove using) and is largely dependent on the subject's ethnicity and clan consanguinity, too. The prevalence of arseniasis in ethnic Han residents was significantly higher than that in their Hmong neighbors (35.0 vs 4.8% OR = 15.18, 95% CI = 3.45-67.35). Notable variances of arseniasis prevalence were observed not only between the ethnic Han clans (G1, G3, and B) and Hmong clan P, but also between different lineages (G1 and G2) inside the ethnic Han clan. Smokers suffered more frequently from arseniasis than non-smokers (47.3 vs 15.7% OR = 5.42, 95% CI = 2.25-12.93). CONCLUSIONS: Arseniasis prevalence in this unique exposure case was impacted by an array of multiple factors. Besides a long-term indoor exposure to As, the ethnicity or the clan consanguinity of exposed subjects may play an important role, too.

Association of XPD/ERCC2 G23591A and A35931C polymorphisms with skin lesion prevalence in a multiethnic, arseniasis-hyperendemic village exposed to indoor combustion of high arsenic coal.

More than 2,000 arsenic-related skin lesions (as at 2002) in a few villages of China's Southwest Guizhou Autonomous Prefecture represent a unique case of endemic arseniasis related with indoor combustion of high-arsenic coal. The skin lesion prevalence was significantly higher in ethnic Han villagers than in ethnic Hmong villagers. This study was focused on a possible involvement of XPD/ERCC2 G23591A and A35931C polymorphisms in risk modulation of skin lesions and in the body burden of As in this unique case of As exposure. G23591A and A35931C were genotyped by a PCR-based procedure. Total As contents in hair and urine samples as well as environmental samples of the homes of the two ethnic clans were analysed. A significant higher presentation of A/A35931 (homozygous wild) genotype in both clans was found in skin lesion patients, compared with their asymptomatic fellow villagers (67.1 vs. 46.3%, OR 2.36, 95% CI 1.35-4.14, P=0.002). Interestingly, the population frequencies of the A/A35931 genotype did not show significant differences between ethnic Han villagers and their Hmong neighbours (47.1 vs. 45.5%). Very low frequencies of homozygous and heterozygous variant genotypes of G23591A were recorded in the residents in target village. G/A23591 and A/A23591 were detected only in 3.2% (8/244) and 0.8% (2/244) of the villagers, respectively. The polymorphic status at the locus of A35931C might modulate the risk for arsenic-related skin lesions in the investigated groups.

Arseniasis prevalence and mortality in a multiethnic, endemic township in Guizhou, China.

OBJECTIVE: Farmers in Southwest Guizhou Autonomous Prefecture, China, represent a unique case of arseniasis, which is related to indoor combustion of high arsenic-containing coal instead of to arsenic-contaminated drinking water. A significant difference in the prevalence of arseniasis was observed in two neighboring ethnic clans in one village. The question arose whether the ethnicity-dependent difference observed in this village was more widely spread throughout the whole township. An epidemiologic investigation was designed to explore arseniasis distribution and mortality among all four ethnic groups in a multiethnic township. METHODS: The cohort of arseniasis patients, diagnosed and registered in the overall field survey of 1991 as well as all the asymptomatic residents of the township, were enrolled in the present investigation. Indirect standardization was used for calculating the age-adjusted standardized incidence ratio (SIR) of arseniasis, the standardized mortality ratio (SMR) of various death causes (including some cancers), and their corresponding intervals of 95% confidence in both genders and in each local ethnic group. RESULTS: The descending rank of arseniasis SIRs among local ethnic groups was found as: Hui>Han>Bouyei>Hmong. The descending rank of SMRs of malignancies was displayed as: Han>Hui>Bouyei>Hmong in males and both genders together as well. Concerning deaths of non-malignant causes the rank was observed as: Hui>Han>Bouyei>Hmong in males. The arseniasis SIR for ethnic Hmong residents (both genders combined) was found to be significantly less profound than the overall level in the township. No death cases in diagnosed ethnic Hmong patients and no cases of death from malignant causes in asymptomatic Hmong residents were recorded. The significant increase of arseniasis prevalence was observed in all males, compared with the overall prevalence of all residents. However, a significantly lower prevalence was seen in all females. CONCLUSION: Significant ethnicity-dependent difference in arseniasis prevalence and mortality from all causes was found in a multiethnic rural township where farmers have been exposed to the indoor combustion of high arsenic coal for decades. The ethnic Hmong residents seemed to be the least susceptible to arseniasis among the four local ethnic groups.

A follow-up study of mortality among the arseniasis patients exposed to indoor combustion of high arsenic coal in Southwest Guizhou Autonomous Prefecture, China.

OBJECTIVE: This study was directed to ascertain the mortality of a group of arseniasis patients in an endemic rural township in Southwest China, where the residents were exposed for decades to indoor combustion of high arsenic coal. METHODS: All the diagnosed arseniasis cases registered in 1991 were defined as the target population, which were assigned to three symptom subgroups by the severity of dermal lesions. The death cases were surveyed and checked. The follow-up period was 12.5 years. The standardized mortality ratio (SMR) of all death causes combined, all cancers combined, and the cancers at every site were analyzed. The age standardized mortality rates (ASMRs) were calculated in three subgroups using the procedure of standardization. RESULTS: One hundred and six death cases were recorded. Liver cirrhosis, non-melanotic skin cancer, lung and liver cancer were the four most prevalent death causes and referred to 70.8% (75/106) of the total death cases. The mortality of all death causes combined was not higher than that of the whole of China in 2001 (SMR = 0.76, 95% CI 0.63-0.93). The crude mortality rate of non-melanotic skin cancer in males reached up to 128.66/10(5). SMRs of lung cancer and larynx cancer in males (SMRs 2.84 and 27.27, 95% CIs 1.51-4.86 and 5.61-79.62, respectively) significantly exceeded the levels for all male Chinese. ASMRs of all death causes combined, all cancers combined and non-melanotic skin cancer in males of the severe dermal symptoms subgroup were significantly higher than those in medium and/or mild dermal symptom subgroups. CONCLUSIONS: A significantly increased mortality due to lung cancer and non-melanotic skin cancer was confirmed, alike the situation in other arseniasis endemic areas in the world. No significant elevation of mortality due to liver cancer and bladder cancer was observed. Male arseniasis patients diagnosed with severe skin lesions face higher risks of malignancies and of non-melanotic skin cancer in particular in the following years.

Glutathione S-transferases M1 and T1 polymorphisms and arsenic content in hair and urine in two ethnic clans exposed to indoor combustion of high arsenic coal in Southwest Guizhou, China.

A total of 2,402 cases of arsenic-related skin lesions (as of 2002) in a few villages of China's Southwest Guizhou Autonomous Prefecture represent a unique case of endemic arseniasis related with indoor combustion of high arsenic coal. A significant difference of skin lesion prevalence was observed between two clans of different ethnicities (Hmong and Han) in one of the hyperendemic villages in this prefecture. This study was focused on a possible involvement of GST T1 and M1 polymorphisms in risk modulation of skin lesions and in the body burden of As in this unique case of As exposure. GST T1 and M1 polymorphisms were genotyped by an allele-specific PCR-based procedure. Total As contents in hair and urine samples as well as environmental samples of the homes of the two ethnic clans were analyzed. No significant deviations in the population frequencies of GST T1 and M1 0/0 genotypes or their combination were recorded between diagnosed skin lesion patients and asymptomatic individuals in both clans. Significantly higher As contents in hair and urine were observed in GSTM1 0/0 carriers, not in GSTT1 0/0 carriers. After stratified by ethnicity and gender, a statistically significant association of the GSTM1 0/0 genotype and higher As content in hair was only confirmed in the subgroups of ethnic Han clan members and all male villagers, not in ethnic Hmong clan members or in females. GST T1 and M1 homozygous deletions were not associated with an increased susceptibility to skin lesions in long-term exposure to indoor combustion of high As coal. The polymorphic status at the locus of GSTM1 might modulate individual's body burden of total As in some Chinese ethnic groups.

Arsenic-related skin lesions and glutathione S-transferase P1 A1578G (Ile105Val) polymorphism in two ethnic clans exposed to indoor combustion of high arsenic coal in one village.

OBJECTIVES: A total of 2402 patients with arsenic-related skin lesions, such as hyperkeratosis, hyperpigmentation or hypopigmentation, or even skin cancer in a few villages in Southwest Guizhou Autonomous Prefecture, China represent a unique case of endemic arsenism related with indoor combustion of high arsenic coal. This study aimed to investigate the cluster of arsenism cases and the possible relevant factors including GSTP1 polymorphism in two clans of different ethnic origin living in one village for generations. METHODS: A questionnaire-based study was performed in 170 Miao clan P members, 10 of whom had arsenic-related skin diseases, and 153 Han clan G1 members, 50 of whom had arsenic-related skin diseases. The data were checked against the registration archives since the 1980s. At the same time, arsenic concentrations in samples of coal, indoor air, drinking water, corn and chilli pepper that were once baked over the stoves for desiccation, as well as in samples of urine and hair of clan members were determined. Glutathione S-transferase P1 (GSTP1) A1578G polymorphism was genotyped by a restriction fragment length polymorphism-based procedure. RESULTS: Arsenism morbidity in Miao clan P was significantly lower than in the neighbouring Han clan G1 [5.9 vs. 32.7%, odds ratio (OR)=0.13, 95% confidence interval (CI): 0.06-0.27, P<0.0001]. No sex differences were confirmed inside both clans. Analyses of the environmental samples indicated that Miao clan P members were exposed to higher amounts of arsenic via inhalation and food ingestion. Hair and urine samples also proved a higher arsenic body burden in ethnic Miao individuals. No corresponding differences by sex were found. Higher frequencies of combined mutant genotype G/G1578 and A/G1578 (OR=4.72, 95% CI: 2.34-9.54, P<0.0001) and of mutant allele G1578 (OR=3.22, 95% CI: 2.00-5.18, P<0.0001) were detected in diagnosed arsenism patients than in non-diseased individuals. The Miao individuals showed a lower percentage of combined mutant genotypes (30.6 vs. 52.7%, OR=0.40, 95% CI: 0.19-0.84, P=0.015) as well as of mutant allele G1578 (OR=0.46, 95% CI: 0.24-0.88, P=0.017) than their Han neighbours. CONCLUSIONS: Genetic predisposition influences dermal arsenism toxicity. The GSTP1 A1578G (Ile105Val) status might be a susceptibility factor for arsenic-related skin lesions.

An association of UDP-glucuronosyltransferase 2B7 C802T (His268Tyr) polymorphism with bladder cancer in benzidine-exposed workers in China.

UDP-Glucuronyltransferase 2B7 (UGT2B7) is involved in benzidine metabolism, as demonstrated by in vitro experiments with liver slices. To evaluate the possible association of UGT2B7 gene polymorphism with bladder cancer risk for benzidine-exposed subjects, diagnosed bladder cancer cases (n = 36) who were members of a cohort of benzidine-exposed workers in the Chinese dyestuff industry were investigated. UGT2B7 polymorphism at locus C802T (His268Tyr) was detected using a PCR-RFLP based procedure. Nondiseased cohort members (156 men, 95 women) were taken as work-related control, and unexposed healthy individuals (113 men, 105 women) were taken as community control. The data showed that the polymorphism at locus UGT2B7 C802T in a general Chinese population significantly differs from that in a Caucasian population (p = 0.00018), displaying a distinctly lower frequency of T/T genotypes (9.2 vs. 25.3%), while no significant difference to a Japanese population could be detected (p = 0.17). A higher prevalence of T/T genotype carriers was found in the cancer cases, compared with unexposed healthy controls (25 vs. 9%, odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.37-7.98, p = 0.006). A higher presentation of T allele carriers in the patients group was also confirmed (46 vs. 33%, OR 1.73, 95% CI 1.05-2.87, p = 0.03). A higher portion of the T/T genotype was also observed in bladder cancer patients compared with nondiseased members of the same benzidine-exposed cohort, although some of them displayed different degrees of cellular alterations in their exfoliated urothelial cells. This study points for the first time to an association between a homozygous mutant genotype of human UDP-glucuronosyltransferase 2B7 catalyzing the biotransformation of benzidine and an elevated bladder cancer risk for formerly benzidine-exposed workers of the dyestuff industry.

Polymorphism of N-acetyltransferase 2 (NAT2) gene polymorphism in shanghai population: occupational and non-occupational bladder cancer patient groups.

OBJECTIVE: Arylamine N-acetyltransferases (NATs) are involved in the detoxification of aromatic amines and hydrazine. In order to explore the possible association of NAT2 polymorphism with bladder cancer risk in benzidine exposed or non-exposed Chinese individuals, healthy subjects, subjects with bladder cancer of a former benzidine exposed cohort in Shanghai dyestuff industry and a group of bladder cancer patients without known occupational exposure to aromatic amines were genotyped for NAT2 gene polymorphism. METHODS: NAT2 genotyping was performed with a set of RFLP procedures at seven major polymorphic loci of gene coding area: G191A, C282T, T341C, C481T, G590A, A803G and G857A. RESULTS: The wild allele NAT2 *4 was the most prevalent allele (59%) in healthy individuals. The alleles NAT2*6A and NAT2*7B were also frequently observed (21% and 17%, respectively). In contrast to Caucasians, the percentage of slow acetylators was lower (12% in Chinese vs. 58% in Caucasians, P < 0.001). No relevant differences were observed for homogenous rapid, heterogeneous rapid/slow and homogeneous slow acetylation genotypes between the healthy subjects and both groups of bladder cancer patients. CONCLUSION: The present work did not support the association of slow acetylating genotypes of NAT2 gene with elevated risk of bladder cancer in Chinese whereas it was documented as an important genetically determined risk factor in Caucasians. Different mechanisms might play a role in individual susceptibility to bladder cancer related with aromatic amine exposure in various races or ethnic groups.

A season-dependent variation of genotoxicity of surface water samples from Taihu Lake, Yangzte delta.

The present study is to assess a year round change of genotoxicity of surface water in Taihu Lake, Yangtze delta. The water samples were collected in spring, summer, autumn and winter of 2001, respectively. The bacterial L-arabinose resistance forward mutation test (ara test), along with the Ames test, was performed for the evaluation of time profile of mutagenicity of the surface water samples. The strong genotoxic potentials were detected in the near-shore area, especially in the vicinity to the major city. All the samples collected from the lake center and areas distant from dense human activity showed genotoxicity-free in year round time. Intensified human activity along the lake may play an important role for the genotoxic pollution. By comparison of the samples from year round, the winter samples showed the strongest mutagenic potential of all seasons, which indicates that meteorological and hydrological factors also affect the water quality. The impact of dense human activity, improper management and season change should be put into consideration for designing an effective remediation project in the lake basin area.

N-Acetyltransferase 2 gene polymorphism in a group of senile dementia patients in Shanghai suburb.

AIM: To investigate the possible association of hereditary polymorphism of N-acetyltransferase 2 (NAT2) gene with the susceptibility towards senile dementia in farmer population of Shanghai suburb. METHODS: NAT2 gene genotyping was performed at 7 major polymorphic loci (G191A, C282T, T341C, C481T, G590A, A803G, and G857A) with a polymerase chain reaction-based restriction fragment length polymorphism based procedure in 2 groups of farmer subjects in Shanghai suburb. A group of 51 diagnosed dementia patients [comprising 29 sporadic Alzheimer disease (AD) patients and 22 sporadic vascular dementia (VD) patients] and a group of 112 healthy individuals were in the same area. RESULTS: The homogenous rapid genotypes (R/R, including*4/*4, *13 /*13, and *4/*13) was found over-present in both groups of patients, compared with healthy individuals, for all farmer dementia patients, 52.9 % vs 33.0 %, P=0.016, OR (95 % CI): 2.28(1.16-4.48); for AD group only, 51.7 % vs 33.0 %, P=0.063, OR (95 % CI): 2.18 (0.95-4.97); for VD group 54.5 % vs 33.0 %, P=0.055, OR (95 % CI): 2.43 (0.96-2.43). The significant frequency difference of genotype *4/*7B between farmer dementia patients and healthy individuals, and that of solo-alleles *13, and *7B were observed between the healthy individuals and both groups of dementia patients. CONCLUSION: Our data suggest the involvement of various NAT2 rapid-acetylating genotypes in the individual susceptibility to senile dementia. Variant genotypes of NAT2 might serve as a hereditary risk factor for AD and VD in Chinese population.

Polymorphism in the N-acetyltransferase 1 alleles NAT1*10 and NAT1*14A and cytological gradings of exfoliated urothelial cells in benzidine-exposed Chinese workers: discussion of ethnic differences.

N-acetyltransferase 1 (NAT1) modifies bladder cancer risk in European populations exposed to aromatic amines in cigarette smoke. The present study was performed to investigate a possible association between NAT1*10 and NAT1*14A genotypes and bladder cancer risk in benzidine-exposed Chinese workers. Based on the cytological gradings of exfoliated urothelial cells according to Papanicolaou, an exposed research cohort was stratified into subgroups. An allele-specific PCR-based procedure was used to detect the polymorphism in the polyadenylation signal at the locus NAT1 T(1088)A. A nested PCR-RFLP procedure was conducted to differentiate NAT1*14A (T(1088)A, C(1095)A, and G(560)A) from NAT1*10 (T(1088)A, C(1095)A). No significantly different frequencies of homozygous and heterozygous NAT1*10 alleles were found among the subgroups with (i) gradings according to Papanicolaou < or = II (18.3 and 40.2%, respectively), (ii) higher gradings according to Papanicolaou (> II; 28.0 and 34.1%, respectively), and (iii) with bladder cancer (26.3 and 34.2%, respectively). The present data show that NAT1*10 neither displayed an association with an elevated grading of urothelial cells nor a clear impact on the risk for bladder cancer in benzidine-exposed Chinese workers. Discrepancies with the findings in European populations could point to ethnic differences in the disposition of aromatic amines.

[Glutathione S-transferase T1, M1 gene polymorphism in leukemia patients in Shanghai area].

OBJECTIVE: To explore the possible association of polymorphisms of glutathione S-transferases T1, M1 genes and leukemia susceptibility. METHODS: AS-PCR procedure was applied to determine the GSTs genotypes in a group of leukemia patients (n=61) in Shanghai area. The genotype frequencies in the leukemia patients and normal controls (183 healthy residents in the same city) were compared. Stratification with leukemia types, age and gender was made for further comparison. RESULTS: The frequencies of GSTT1 0/0 genotype and GSTT1 0/0-GSTM1 0/0 combined genotype were higher in leukemia patients than in controls, and the differences were significant. When stratified with age and gender, this trend still existed in the male ALL patients and in younger ALL patients (age < or = 30). CONCLUSION: Individuals who bear GSTT1 0/0 genotype or GSTT1 0/0-GSTM1 0/0 combined genotypes are more susceptible to leukemia, especially for male and younger carriers.

Polymorphism of alpha-estrogen receptor and aryl hydrocarbon receptor genes in dementia patients in Shanghai suburb.

AIM: To explore the possible association of different polymorphic forms of human alpha-estrogen receptor (ER-alpha) and aryl hydrocarbon receptor gene (Ahr) with the risk to senile dementia in farmers in Shanghai suburb. METHODS: Senile dementia patients (n=52) were examined for ER-alpha and Ahr gene polymorphism genotyping. Healthy individuals (n=125) in the same area were selected as a community control group. Two polymorphic loci, Pvu II locus and Xba I locus, of human ER- a gene were investigated by a PCR-RFLP-based procedure. The population frequencies of two polymorphic loci in exon 10 of Ahr gene, G1721A (R554K) and G1768A (V570I) were compared between patients and healthy controls using an allele-specific PCR (AS-PCR) procedure. RESULTS: The mutant allele frequencies of ER-alpha gene in the AD group were significantly higher than those in the control group (P=0.023, OR=2.94, 95 % CI 1.13-7.71 for Pvu II locus; P=0.046, OR=2.28, 95 % CI 1.003-5.17 for Xba I locus). The mutant allele frequencies among female AD patients were higher than those in the female controls (P=0.016, OR=3.68, 95 % CI 1.22-11.08 for Pvu II locus, P=0.029, OR=2.95, 95 % CI 1.10-7.94 for Xba I locus). The mutant form, neither in the homozygous, nor in the heterozygous form was detected at the locus of Ahr G1768A in a normal local population. No significant difference of Ahr genotype frequency at locus G1721A was noticed between the patients and healthy individuals. CONCLUSION: The distribution of ER polymorphisms was significantly different between Chinese and some other ethnic populations. The results suggested that ER-alpha gene polymorphisms might be related to the individual susceptibility to AD, especially in the females. However, it did not support the association of Ahr gene polymorphism with higher risk of senile dementia.

The mutagenic potentials of tap water samples in Shanghai.

The tap water samples were collected from the users' ends in several areas of Shanghai, which is located in Taihu Lake basin, Eastern China. Source water samples were also collected from two municipal source water facilities at the same time. Samples were assayed by three different short-term mutagenicity test systems: Salmonella/microsome assay (Ames test), the Arabinose resistance test (Ara test) and the SOS/umu test. The data showed that two source water samples did not display direct mutagenic potentials. Two tap water samples from city north, which were directly from Yangtze River, were also not mutagenic. Water samples from city south and middle which used source water originating from Taihu Lake were proved to be contaminated with mutagenic potentials by three different assay techniques. The boiled water displayed an even stronger mutagenic potential compared to its original tap water. The molecular mechanism of mutagenicity was associated with a reading frame-shifting potential. GC-MS analysis of tap water extracts from city middle and corresponding source water was compared. Qualitatively similar spectra were observed except for the peaks of three chlorinated aromatic hydrocarbon compounds, which existed only in the tap water. Since the water source has been polluted, raw water was heavily chlorinated in order to sterilize. More toxic compounds, including mutagens, might form during the multi-chlorination. Caution about the possibility of elevated cancer risks in the population that consumes heavily chlorinated water should be kept in mind. A cohort study in the residents of Shanghai is required.

Polymorphism of glutathione S-transferase T1, M1 and P1 genes in a Shanghai population: patients with occupational or non-occupational bladder cancer.

OBJECTIVE: Glutathione S-transferases are involved in the conjugation of xenobiotics. To explore whether GSTs polymorphisms are involved in the development of occupational or non-occupational bladder cancer, polymorphism frequencies of GSTT1, M1 and P1 were investigated in a normal population, which had been settled in a rural area in Shanghai suburb for at least 5 generations as well as in a group of patients with benzidine exposure related occupational bladder cancer in Shanghai dyestuff industry and a group of patients with non-occupational bladder cancer. METHODS: PCR based procedures were performed in the study populations to confirm the genotypes of GSTT1, M1 and P1. RESULTS: The polymorphisms at locus of GSTP1-A1578G in the normal population differed significantly from those in Caucasians or African Americans. All the subjects genotyped so far (n = 118) bore only homogenous wild genotype (C2293/C2293) at GSTP1-C2293T locus. This locus seemed to be a monomorphic in Shanghai population. No significant difference in GSTT1 and GSTM1 polymorphic form frequencies could be confirmed among three groups of subjects. An overrepresentation of GSTP1 AG or GG genotype corresponding a less stable and less effective isozyme protein was detected in patients with benzidine related occupational bladder cancer, compared with that in the normal population though a statistical significance was not yet reached (P = 0.09, OR = 1.96, 95% CI 0.89-4.32). CONCLUSION: This study suggests that GSTM1 or GSTT1 homozygous deficiency genotypes and their combination do not have a clear impact on bladder cancer incidence in a Shanghai population. It seems that GSTP1 polymorphism is not associated with non-occupational bladder cancer. GSTP1 AG or GG genotype has a higher frequency in the patients with benzidine related occupational bladder cancer, and further work is needed to confirm if GSTP1 AG or GG genotype plays a role in the development of occupational bladder cancer.

Nonassociation of aryl hydrocarbon receptor genotypes with susceptibility to bladder cancer in Shanghai population.

AIM: To assess two polymorphic forms of aryl hydrocarbon receptor (AHR) gene, G1721A (R554K), and G1768A (V570I) in Chinese population and to explore the possible association of human AHR gene polymorphism with elevated incidence of bladder cancer among Chinese Han subjects in east of China. METHODS: An allele specific PCR-based procedure for AHR gene polymorphism genotyping was developed by this work. Genotyping on three groups of subjects in Shanghai area had been performed: a bladder cancer group with the occupational exposure to benzidine, a non-occupational bladder cancer patient group whose members lack an obvious aromatic amine exposure record, and a normal population in the same city as controls. RESULTS: A significant difference (P < 0.01) in frequency distribution at locus G1721A between normal population in Shanghai and a Caucasian population reported by other authors was observed. No mutant allele(A1768) at locus G1768A had ever been detected in our study. The observed frequencies were similar between both genders in the normal population (P = 0.54), and there were no significant difference confirmed between the case group and the control group. CONCLUSION: The locus G1768 of human AHR gene seems to be monomorphic among Chinese in this area. The significant distribution difference at locus G1721A of human AHR gene between Chinese Han and Caucasian was confirmed. This study did not support the association of AHR G1721A polymorphism with higher risk to bladder cancer among the residents in this area, either in a group of occupationally benzidine-exposed individuals or among the persons who never have an obvious aromatic amine exposure record.