Source of drinking water at home and site-specific cancer incidence in Washington County, Maryland

A nonconcurrent prospective study was conducted to investigate the postulated relationship between organic chemical by-products of water chlorination and risk of human cancer. Vital records and nonofficial census data available for each of nearly 31,000 study subjects were used to compute selected sex- and site-specific cancer incidence rates in a well-defined county population. Age, socioeconomic status, smoking history, source of drinking water at home, and other individual characteristics of the study population were examined in relation to the cancer rates. The drinking water source variable consisted of three historical cohorts, each distinguished by a different degree of exposure to chloroform and other chlorination byproducts. Incidence rates for cancer of the bladder among men and for cancer of the liver among women were nearly twofold higher in the drinking water cohort that had been supplied chlorinated surface water at home when compared to the cohort with a history of consumption of unchlorinated ground water. The differences, however, were not statistically significant. A complementary mortality study also suggested an association of chlorinated water with cancer of the liver and urinary tract. The findings in Washington County indicate the need for further studies of individuals with different histories of exposure to chlorinated and unchlorinated drinking water.     

Sister chromatid exchanges in Vicia faba induced by arsenic-contaminated drinking water from Zimapan, Hidalgo, Mexico

Sister chromatid exchanges (SCE) in Vicia faba root tips were used to examine well water containing high levels of arsenic. The increased amount of arsenic was contained in well water from different towns of Zimapan, Hidalgo, Mexico. Treatments of 3 h were applied followed by the differential staining technique of Tempelaar et al. (Mutation Res. 103 (1982) 321-326). Concentrations of arsenic from 0.267 up to 1.070 mg/l were determined by colorimetry in the polluted samples used for this study. These values were above the permissible limit of 0.05 mg/l in drinking water. In all cases, except one in which the As concentration was 0.021, the arsenic-contaminated water produced significant increases of SCE compared with the control (p < 0.001) and a concentration-response relationship was observed. The SCE potency factor of 33 per mg/l of arsenic was calculated as the slope of a common regression line, pooling data previously obtained in the Comarca Lagunera and the results observed in Zimapan.     

Assessment of the carcinogenic potential of chlorinated water: experimental studies of chlorine, chloramine, and trihalomethanes

BACKGROUND: Water chlorination has been one of the major disease prevention treatments of this century. While epidemiologic studies suggest an association between cancer in humans and consumption of chlorination byproducts in drinking water, these studies have not been adequate to draw definite conclusions about the carcinogenic potential of the individual byproducts. PURPOSE: The purpose of this study was to investigate the carcinogenic potential of chlorinated or chloraminated drinking water and of four organic trihalomethane byproducts of chlorination (chloroform, bromodichloromethane, chlorodibromomethane, and bromoform) in rats and mice. METHODS: Bromodichloromethane, chlorodibromomethane, bromoform, chlorine, or chloramine was administered to both sexes of F344/N rats and (C57BL/6 x C3H)F1 mice (hereafter called B6C3F1 mice). Chloroform was given to both sexes of Osborne-Mendel rats and B6C3F1 mice. Chlorine or chloramine was administered daily in the drinking water for 2 years at doses ranging from 0.05 to 0.3 mmol/kg per day. The trihalomethanes were administered by gavage in corn oil at doses ranging from 0.15 to 4.0 mmol/kg per day for 2 years, with the exception of chloroform, which was given for 78 weeks. RESULTS: The trihalomethanes were carcinogenic in the liver, kidney, and/or intestine of rodents. There was equivocal evidence for carcinogenicity in female rats that received chlorinated or chloraminated drinking water; this evidence was based on a marginal increase in the incidence of mononuclear cell leukemia. Rodents were generally exposed to lower doses of chlorine and chloramine than to the trihalomethanes, but the doses in these studies were the maximum that the animals would consume in the drinking water. The highest doses used in the chlorine and chloramine studies were equivalent to a daily gavage dose of bromodichloromethane that induced neoplasms of the large intestine in rats. In contrast to the results with the trihalomethanes, administration of chlorine or chloramine did not cause a clear carcinogenic response in rats or mice after long-term exposure. CONCLUSION: These results suggest that organic byproducts of chlorination are the chemicals of greatest concern in assessment of the carcinogenic potential of chlorinated drinking water.     

Effects of dichloroacetate on glycogen metabolism in B6C3F1 mice

Dichloroacetate (DCA) is a by-product of drinking water chlorination. Administration of DCA in drinking water results in accumulation of glycogen in the liver of B6C3F1 mice. To investigate the processes affecting liver glycogen accumulation, male B6C3F1 mice were administered DCA in drinking water at levels varying from 0.1 to 3 g/l for up to 8 weeks. Liver glycogen synthase (GS) and glycogen phosphorylase (GP) activities, liver glycogen content, serum glucose and insulin levels were analyzed. To determine whether effects were primary or attributable to increased glycogen synthesis, some mice were fasted and administered a glucose challenge (20 min before sacrifice). DCA treatments in drinking water caused glycogen accumulation in a dose-dependent manner. The DCA treatment in drinking water suppressed the activity ratio of GS measured in mice sacrificed at 9:00 AM, but not at 3:00 AM. However, net glycogen synthesis after glucose challenge was increased with DCA treatments for 1-2 weeks duration, but the effect was no longer observed at 8 weeks. Degradation of glycogen by fasting decreased progressively as the treatment period was increased, and no longer occurred at 8 weeks. A shift of the liver glycogen-iodine spectrum from DCA-treated mice was observed relative to that of control mice, suggesting a change in the physical form of glycogen. These data suggest that DCA-induced glycogen accumulation at high doses is related to decreases in the degradation rate. When DCA was administered by single intraperitoneal (i.p.) injection to na?ve mice at doses of 2-200 mg/kg at the time of glucose challenge, a biphasic response was observed. Doses of 10-25 mg/kg increased both plasma glucose and insulin concentrations. In contrast, very high i.p. doses of DCA (> 75 mg/kg) produced progressive decreases in serum glucose and glycogen deposition in the liver. Since the blood levels of DCA produced by these higher i.p. doses were significantly higher than observed with drinking water treatment, we conclude that apparent differences with data of previous investigations is related to substantial differences in systemic dose and/or dose-time relations.     

分光光度法测定生活饮用水中挥发性酚类物质的研究

总结了按国家标准方法（4－氯基安替比林分光光度法）测定生活饮用水中挥发性酚类物质的技术操作要领,以及对方法测定原理的理解和体会,且注重实际操作,对有关分析人员具有一定的参考作用。     

Subtle neurological deficits and psychopathological findings in substance-abusing homeless and non-homeless veterans

PROBLEM: In vitro studies have demonstrated microfractures in resected roots after root end cavity preparation with ultrasonic tips. Such microfractures are of concern; however, they may be artifacts. OBJECTIVES: To assess the incidence of microfractures after ultrasonic root end cavity preparation in situ. STUDY DESIGN: Fifty-two roots in two cadavers were endodontically treated, the soft tissues excised, and the root ends exposed and resected. The resected root surfaces were replicated with polyvinylsiloxane impressions. Root end cavities were prepared with ultrasonic tips, then impressed a second time. The roots were retrieved; 25 were processed for direct SEM examination as were both the impressions of each root. The specimens were examined by stereomicroscope and scanning electron microscope. RESULTS: In the impressions, the resected and prepared surfaces appeared irregular, but none demonstrated microfractures. In contrast, 15 retrieved roots showed microfractures. CONCLUSIONS: Ultrasonic root end cavity preparation in situ did not cause root microfractures, and the impression technique could be clinically usable with minor modifications.     

Promotion of rat hepatocarcinogenesis by dimethylarsinic acid: association with elevated ornithine decarboxylase activity and formation of 8-hydroxydeoxyguanosine in the liver

Arsenicals are epidemiologically significant chemicals in relation to induction of liver cancer in man. In the present study, we investigated the dose-dependent promotion potential of dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenicals in mammals, in a rat liver carcinogenesis model. In experiment 1, glutathione-S-transferase placental form (GST-P)-positive foci, putative preneoplastic lesions, were employed as endpoints of a liver medium-term bioassay for carcinogens (Ito test). Starting 2 weeks after initiation with diethylnitrosamine, male F344 rats were treated with 0, 25, 50 or 100 ppm of DMAA in the drinking water for 6 weeks. All animals underwent two-thirds partial hepatectomy at week 3 after initiation. Examination of liver sections after termination at 8 weeks revealed dose-dependent increases in the numbers and areas of GST-P-positive foci in DMAA-treated rats as compared with controls. In experiment 2, ornithine decarboxylase activity, which is a biomarker of cell proliferation, was found to be significantly increased in the livers of rats treated with DMAA. In experiment 3, formation of 8-hydroxydeoxyguanosine, which is a marker of oxygen radical-mediated DNA damage, was significantly increased after administration of DMAA. These results indicate that DMAA has the potential to promote rat liver carcinogenesis, possibly via a mechanism involving stimulation of cell proliferation and DNA damage caused by oxygen radicals.     

Drinking water supply with reference to geogenic arsenic contamination

Geogenic Arsenic in Drinking Water. Drinking water production of surface spring water in southern Lower Saxony (Niedersachsen, Germany) was reduced because of microbiological contaminations and unreliably variable water reserves. Surface spring water in general has a low arsenic content. As a consequence ground water has been increasingly used for drinking water. Thus, high geogenic concentrations of arsenic in the central "Buntsandstein" in southern Lower Saxony caused high arsenic contents in the groundwater. Under the regulation of the German Drinking Water Ordinance (1986) the limit for total arsenic (40 micrograms/l) was exceeded in 2% of 150 fountains, wells and sources in southern Lower Saxony. Because of the well-known cancerogenic potential of arsenic the limit for total arsenic in drinking water was reduced from 40 micrograms/l to 10 micrograms/l suspending the new standard value until January 1996. This regulation based on new calculations revealing a skin cancer risk of roughly 6:10,000 and a mortality risk of roughly 1:10(6) in respect of lifetime in case of arsenic concentrations of 10 micrograms As/l drinking water. After that limit change 40% of 150 wells and sources in southern Lower Saxony exceeded the arsenic limit of 10 micrograms/l drinking water. As a matter of fact, it became necessary for a large number of water supply works to eliminate arsenic from the drinking water by technical means or to dilute drinking water with high concentrations of arsenic.     

Methotrexate suppresses nitric oxide production ex vivo in macrophages from rats with adjuvant-induced arthritis

This review discusses the relation between by-products of drinking water chlorination and cancer in the light of present toxicological and epidemiologic evidence. During the chlorination of drinking water, a complex mixture of by-products forms from chlorine and the organic and inorganic compounds present in raw water. The quality and quantity of such compounds depend on the specific nature of the organic material in raw waters, the inorganic material in raw water, pH, temperature, other water treatment practices, and the chlorine timing and dose added. Chlorination by-products are important mainly when surface water is used for drinking water as more organic compounds are present in surface waters than in ground waters. The gastrointestinal and urinary tract are the cancer sites that are most often associated with the use of chlorinated surface water or with the quantity of chlorination by-products in the water-supply network. Yet the microbial quality of drinking water should not be compromised by excessive caution over the potential long-term effects of disinfection by-products because the risk of illness and death resulting from exposure to pathogens in untreated drinking water may be several orders of magnitude greater than the cancer risks from chlorination by-products.     

Aromatase cytochrome P450 transcripts are detected in fractured human bone but not in normal skeletal tissue

Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are metabolites of the industrial solvent and environmental contaminant trichloroethylene (TCE), as well as contaminants of chlorinated drinking water. Human exposure to these chemicals is of concern as all three have been shown to increase liver tumor incidence in mice. Differences in dose-response curves, progression to cancer, and postexposure regression of lesions suggest that TCA and DCA work through different mechanisms. The purpose of this study was to further characterize the proliferative hepatocellular lesions promoted by TCA and DCA using biomarkers of cell growth, differentiation, and metabolism in liver sections to better delineate the distinctions in the mechanism of the two chloroacetates. Fifteen-day-old female mice were initiated with 25 mg/kg N-methyl-N-nitrosourea. The initiated mice were administered DCA or TCA (20.0 mmol/L) in drinking water from age 49 days until euthanasia at age 413 days. The pathologic assessment showed that the foci of altered hepatocytes and tumors occurring in the animals promoted with DCA were eosinophilic and positive immunohistochemically for TGF-alpha, c-jun, c-myc, CYP 2E1, CYP 4A1, and glutathione S-transferase-pi (GST-pi). The DCA lesions also were essentially negative for c-fos and TGF-beta, but nontumor hepatocytes were consistently TGF-beta-positive. In contrast, tumors promoted by TCA were predominantly basophilic, lacked GST-pi, and stained variably; usually, more than 50% of the tumor hepatocytes were essentially negative for the other biomarkers. This study demonstrates some striking differences in certain molecular biomarkers of cell growth, differentiation, and metabolism between DCA and TCA. The results also suggest some potential growth signal transduction pathways that may contribute to the DCA promotion of tumors, further support the premise that these two chloroacetates promote hepatocarcinogenesis in different ways, and provide a rational basis for a similar comparison with TCE. Such a comparison should give some insight as to whether DCA, TCA, or both are playing a significant role in the murine liver carcinogenesis of the parent compound, TCE.     

Emotions, stress, smoking, alcohol consumption and cancer--the correlational and causal connections

Correlative and causal relationships are discussed between emotions, stress, smoking, drinking, and cancer. The following conclusions have been drawn. Emotions control the physiological stress reactions: the negative emotions initiate and maintain stress, and positive emotions stop it. A dissatisfied need provokes the development of the state of emotional stress. There are two types of emotional stress states: the active stress which is directed to "overcoming" and the passive state of "waiting till the stress is over". Individuals differ in emotionality, stress reactivity, and inclination to the active and passive emotional stress. The passive emotional stress increases the probability of cancer. This effect is caused by the development of the hormonal and neurotransmitter state, which provokes immunosuppression, DNA damage, and stimulation of hemopoiesis. Smoking and drinking are the ways of modifying the psychoemotional state. These habits as well as development of cancer are the effects of the same cause--stress. Thus, cases of correlation between smoking and drinking do not reflect the causal relationships. Only intensive smoking and drinking which lead to tissue damage can increase the incidence of cancer.     

Inhibitory effect of the non-steroidal anti-inflammatory drugs, indomethacin and piroxicam on 2-acetylaminofluorene-induced hepatocarcinogenesis in male ACI/N rats

The modifying effects of the non-steroidal anti-inflammatory drugs, indomethacin (IMC) and piroxicam (PC) on hepatocarcinogenesis induced by 2-acetylaminofluorene (AAF) were investigated in male ACI/N rats. Rats were divided into 6 groups: group 1 was fed a diet containing 200 ppm AAF for 16 weeks, starting at 6 weeks of age; group 2 was fed an AAF together with 130 ppm PC-containing diet; group 3 received an AAF diet and IMC (10 ppm) in their drinking water; group 4 was fed a PC diet alone; group 5 was given IMC alone; and group 6 served as controls. The PC diet, or the drinking water containing IMC, was given to the rats starting at 5 weeks of age until 1 week after the carcinogen exposure. At termination of the experiment (week 36), the incidences of iron-excluding altered liver cell foci (24.2 +/- 5.2/cm2) and liver cell tumors (1/10, 10%), and the tumor multiplicity (0.10/rat) in rats of group 2 were significantly smaller than those of group 1 (foci incidence, 42.6 +/- 6.7/cm2; tumor incidence, 10/10, 100%; and multiplicity, 4.00/rat) (P < 0.05). Similarly, the incidence of iron-excluding hepatocellular foci (27.4 < 1.2/cm2) and liver cell tumors (1/10, 10%) and the tumor multiplicity (0.10/rat) in rats of group 3 were significantly lower than those of group 1 (P < 0.05). There were no liver cell lesions (foci and neoplasms) in rats of groups 4, 5 and 6. Thus, PC and IMC inhibited the hepatocarcinogenesis induced by AAF when administered concurrently with the carcinogen and the results may indicate possible involvement of altered arachidonic metabolism in the initiation phase of AAF-induced liver carcinogenesis.     

Calcium and magnesium in drinking water and risk of death from rectal cancer

The possible association between the risk of rectal cancer and the levels of calcium and magnesium in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible rectal-cancer deaths (986 cases) of Taiwan residents from 1990 through 1994 were compared with a sample of deaths from other causes (986 controls), and the levels of calcium and magnesium in the drinking water of these residents were determined. Data on calcium and magnesium levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes, and the controls were pair-matched to the cases by gender, year of birth and year of death. Compared with those with calcium levels below 22.0 mg/liter, the adjusted odd ratios (95% confidence interval) were 0.72 (0.53-0.98) for the group with water calcium levels between 22.0 and 40.8 mg/liter and 0.63 (0.45-0.87) for the group with calcium levels of 40.9 mg/liter or more. The adjusted odd ratios were not statistically significant for the relationship between magnesium levels in drinking water and rectal cancer. The results of the present study show that there may be a significant protective effect of calcium intake from drinking water on the risk of rectal cancer.     

Centrally mediated hypocholesterolaemic response of insulin in dogs

Insulin on intravenous administration in dogs caused a rise in blood cholesterol level. This may be due to its direct action on liver or other peripheral structures. On the other hand, insulin administered into the lateral cerebral ventricles in normal as well as in spinal and vagotomized dogs resulted in a lowering of blood cholesterol. In cross circulation studies insulin administered into lateral cerebral ventricles of donor dogs produced a hypocholesterolaemia in the recepient dogs without significant changes in blood cholesterol of donor dogs. It is suggested that some substance may be liberated from some parts of central nervous system due to an action of centrally administered insulin. This substance in turn causes hypocholesterolaemia by acting on liver or some other peripheral structures in dogs.     

Performance and mood during and after gradual sleep reduction

Angiotensin is a potent dipsogenic substance and causes elevated water intake in some pathological conditions but as yet no physiological role for angiotensin in normal thirst has been proven. If angiotensin is important in normal drinking, then it should contribute to the drinking which follows water deprivation. The rehydration of bilaterally nephrectomized rats, rats with bilateral ureteric ligation and control rats was compared after 21 hours of water deprivation. The total intake during the 6 hour rehydration was the same in the 3 groups despite the differences in the level of circulating angiotensin. Thus the renal renin-angiotensin system is not essential for deprivation-induced drinking. Another way to test any contribution to drinking by angiotensin is the administration of the competitive angiotensin inhibitor, saralasin acetate. In a control experiment saralasin acetate was found to block the dipsogenic effect of intravenous angiotensin. The infusion of saralasin acetate in a wide range of doses did not, however, affect the drinking following ligation of the inferior vena cava. Thus angiotensin is not essential for drinking following caval ligation. Two possible explanations for these results are that angiotensin is not normally involved in these types of thirst or that there is redundancy in the control of drinking with compensation for blocked mechanisms.     

Crystal structure of the actin-binding protein actophorin from Acanthamoeba

Tertiary butyl alcohol and trichloroacetic acid are known to be contaminants in drinking water. In order to evaluate the interactive toxicity of t-butyl alcohol with trichloroacetic acid, young male Wistar rats were dosed through water at a dose level of t-butyl alcohol (TBA)-0.5% (v/v), trichloroacetic acid (TCA)-25 ppm and a combined dose of TBA + TCA (0.5% v/v TBA-25 ppm TCA) for a period of 10 weeks ad libitum and were maintained on normal diet. The control animals received plain water and normal diet. The liver and kidney histology was undertaken to see whether subtoxic administration of TBA and TCA individually as well as combined administration for a period of 10 weeks would bring about any histological alterations. It was observed that TBA, TCA and TBA + TCA caused histological alterations in the liver such as centrilobular necrosis, vacuolation in hepatocytes and loss of hepatic architecture. TBA and TBA + TCA caused periportal proliferation and lymphocytic infiltration. Hypertrophy of hepatocytes in the periportal area was a characteristic feature in the liver of TCA treated rats. Moreover, in the histology of the kidney, in the three treated groups, degeneration of renal tubules, with syncitial arrangements of the nucleus of renal tubular epithelial cells was evident. In addition to this, degeneration of the basement membrane of the Bowmans capsule, diffused glomeruli and vacuolation of glomeruli was also evident in the three treated rat kidneys. Renal tubular proliferation in certain areas was also evident in certain areas of the kidney in TCA treated rats. The results indicate that, TBA and TCA do bring about alterations in histology of liver and kidney, but on combined administration, do not show enhanced toxicity in the form of increased hepatic and renal injury.     

Changes within vascular bundles of rodent kidneys caused by different diets

Morphological effects caused by two different diets (low protein-high water intake, and high protein-restricted water) on the vascular bundles in the outer medullary zone of the kidney were studied in the laboratory white mouse and in the golden spiny mouse (Acomys russatus, Muridae). In both rodents, when on a low protein-high water intake diet, considerable interstitial substance was found between the vasa recta of the bundles. No interstitial substance was found in animals on high protein-low water intake diet; as a result the vasa recta of the vascular bundle adhered closely. The low protein-high water intake diet caused a marked diuresis, low urine osmolality and low urinary urea concentration. It is assumed that the increase in interstitial substance between the vasa recta of the vascular bundle lowers the efficiency of the counter current barrier system for urea in the kidney and, as a consequence, the medullary urea gradient and urine concentrating capacity decreases. In animals on a high protein diet, the closely juxtaposed vasa recta assure an efficient countercurrent exchange, leading to accumulation and maintenance of a large urea gradient in the medulla and maximal urine concentration. It is suggested that the amount of interstitial material between the vasa recta of the vascular bundle might serve as a modulating factor for the urea concentration in the kidney.     

德兴铜矿生活饮用水源中铁、锰含量的调查及提高水质的对策

德兴铜矿生活饮用水源来自于婺源叶坑水库和乐安江,由于乐安江水质不定期受到污染,主要危害物质是挥发酚等有机毒物,因此德兴铜矿自来水公司主要取用叶坑水库水作为生活饮用水。而叶坑水库水随季节的变化,铁、锰含量的变化较大,有时超标严重,有时符合标准,经过2年的调查研究,总结了铁、锰含量随季节变化的规律,从而在水处理过程中采取了相应的对策,确保了出厂净化水符合国家生活饮用水卫生标准,维护了生活在德兴铜矿地区、六、七万居民的饮水安全。     

Angiotensin-converting enzyme in subfornical organ mediates captopril-induced drinking.

These experiments tested whether angiotensin-converting enzyme (ACE) located within the subfornical organ (SFO) participates in the generation of water intake during peripheral ACE blockade with captopril (CAP). Lesions of the SFO virtually abolished drinking in response to intraperitoneal CAP injection. Intracranially injected CAP suppressed drinking induced by intraperitoneal CAP more completely with direct SFO injection compared with intraventricular or control tissue injections. This central captopril treatment did not alter the drinking response to subcutaneous hypertonic saline. Intraventricular injections of the angiotensin II (ANG II) receptor blocker sarile reduced drinking during oral captopril treatment in rats rehydrating from water deprivation. The results indicate that (a) the SFO mediates drinking caused by peripheral ACE inhibition; (b) the ACE located within the SFO may locally convert ANG I to ANG II, which then stimulates thirst; and (c) central ANG II receptors mediate thirst caused by peripheral ACE inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)