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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxic cyanobacterial blooms are an increasing problem in Poland. The production of cyanobacterial toxins and their presence in drinking and recreational waters represent a growing danger to human and animal health. This is connected with the increase of cyanobacterial biomass caused by excessive eutrophication of the water ecosystem. There is evidence that cyanobacterial hepatotoxins can act as a potent promoter of primary liver cancer. The apoptotic effect of microcystins in Polish cyanobacterial bloom samples on rat hepatocytes and human lymphocytes was observed using light and fluorescence microscopy, flow cytometry, and electrophoretic analysis. The incubation time needed to observe the first morphological apoptotic changes in hepatocytes was approximately 30 min; however, the characteristic biochemical changes in DNA were not observed even after 120 min. In lymphocyte cultures the morphological changes characteristic for apoptosis were observed after 24 h of incubation and a 48-h incubation was found to be optimal for analysis of internucleosomal DNA fragmentation, which is one of the main biochemical hallmarks of programmed cell death. These cells are an easily isolated and inexpensive material for medical diagnostics. Therefore the apoptotic changes, together with the clastogenic effect seen in lymphocyte cultures, are proposed as a future analytical method for these toxins.
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PMID:Apoptotic effect of cyanobacterial extract on rat hepatocytes and human lymphocytes. 1140 94

Tamoxifen is a potent rat liver carcinogen, currently being used as a long-term chemopreventative for breast cancer in healthy women. The mechanism by which tamoxifen causes liver cancer in rats is known to be associated with the accumulation of tamoxifen DNA adducts in this organ. We have examined the dose-response relationship of tamoxifen-induced DNA adducts in the liver and the subsequent increase in the development of liver cancer, with and without phenobarbital promotion. Female Wistar (Han) rats were fed 420 ppm tamoxifen in the diet for 0, 1, 4, 8 or 12 weeks after which time rats were either examined immediately for hepatic tamoxifen-induced DNA damage using the 32P-Postlabelling assay, or left for lifetime for tumour assessment. A proportion of rats left for lifetime study were given phenobarbital in their drinking water. There was a clear dose-response relationship with respect to duration of tamoxifen exposure for both accumulation of DNA adducts and lifetime risk of liver cancer. In the absence of phenobarbital promotion there was a threshold value for tamoxifen-induced DNA adducts (180 adducts/10(8) nucleotides) and the subsequent induction of liver cancer. This study demonstrates the relationship between the accumulation of hepatic tamoxifen-induced DNA adducts and the development of liver cancer and establishes the threshold for hepatocarcinogenesis in terms of DNA adduct formation. These data could provide useful information in interpreting the relevance of low levels of DNA adducts in humans.
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PMID:Cumulative exposure to tamoxifen: DNA adducts and liver cancer in the rat. 1157 Jun 96

Cyanobacterial blooms occur worldwide and present an increasing problem due to eutrophication of lakes. Microcystins, especially microcystin-LR, are microcyclic heptapeptide hepatotoxins and are the most common and potent toxins associated with cyanobacteria. Microcystin is rapidly taken up by hepatocytes through carrier-mediated transport. Once in the hepatocyte, microcystin causes structural damage to the cell indirectly by inhibiting protein phosphorylases 1 and 2A, which are needed for regulation of structural proteins of the cell. Acute liver hemorrhage and death occur with high doses of microcystin-LR, which is also a potent tumor promoter in laboratory rats. The significance of microcystin to human health has been debated; however, poisoning in humans has occurred due to contaminated dialysis water. Microcystin in contaminated drinking water may be the cause of elevated rates of primary liver cancer in some areas of China. Problems with hepatotoxic cyanobacteria have been most seen in livestock. Treatment of confirmed microcystin toxicosis in livestock is likely to be unrewarding, so prevention is important. Wild mammals, birds, fish, insects, and microinvertebrates may also be affected by microcystin.
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PMID:The toxicology of microcystin-LR: occurrence, toxicokinetics, toxicodynamics, diagnosis and treatment. 1157 38

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N(7)-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N(7)-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.
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PMID:Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. 1172 48

Heterocyclic compounds by far outnumber the homocyclic PAHs. In addition, they are often more soluble in water, which may imply a greater biological significance of these heterocycles. Yet, most research focuses on the homocyclics, based on the implicit assumption that the mostly higher concentration of the homocyclics rank these compounds as priority compounds. This review critically examines the available evidence and poses questions on the biological activity and environmental risk of one small group of heterocyclics, the azaarenes, which contain one nitrogen atom in one of the aromatic rings. In different sections, the biotransformation and different types of toxicity are discussed in comparison to those of homocyclic PAHs. The last section focuses on the implications for risk assessment of PAHs. Two- and three-ringed azaarenes can be relatively easily transformed by bacteria, fungi, invertebrates, and vertebrates. The presence of the N-moiety in the smaller azaarenes leads to metabolic routes that partly differ from those of the homoaromatic analogues. Major metabolic products of the azaarenes appear to be ketones and mono- or dihydroxylated azaarenes. Microorganisms can further degrade these into multiple oxygen-containing compounds or they can open up the aza-containing aromatic ring and fully metabolize the products. Fungi and vertebrates were shown to produce the mutagenic dihydrodiol metabolites. The metabolism of the larger azaarenes in vertebrates proceeds analogous to homoaromatic PAH, because in these larger molecules the N-moiety has less influence. Transformation of the larger azaarenes by microorganisms proceeds much slower if occurring at all. Direct toxicity data of azaarenes are mostly restricted to the effects of acridine and quinoline on a relatively small number of species. From this limited set it becomes clear that differences between species are relatively small. As with homocyclic PAHs, toxicity generally increases with increasing number of rings, and baseline toxicity models based on homocyclic PAHs do apply. Toxicity differences between isomers indicate that azaarene toxicity cannot be explained by molecular size-related parameters alone, indicating that electronic forces may be important as well. Considering chronic toxicity it becomes clear that the often-used acute-to-chronic-ratios often underestimate specific chronic toxicity, even within the very limited set of chronic data available. In contrast with homocyclic PAHs, photodegradation of azaarenes shows the same degradation products as biological transformation involving monooxygenases. In general, as for homocyclic PAHs, the degree of phototoxicity is related to the UV absorption characteristics of the azaarenes, which makes it possible to apply the QSAR models developed for homocyclic PAHs to azaarenes as well. Recent research on algae showed that UV-A is the main cause of photoenhanced toxicity. Together with the fact that in the water column UV-B is almost absent, this clearly demonstrates the relevance of phototoxicity in the field. Mutagenicity of azaarenes generally proceeds through similar pathways as in homocyclic PAHs, with bay region diol epoxides as major genotoxic metabolites. The N-moiety can, however, result in differences in genotoxic activities between isomers. Carcinogenicity of azaarenes in mammals is generally restricted to four-ringed and larger structures, and mechanisms leading to cancer are similar to those of homocyclic aromatics. An exception to this general pattern is quinoline, which has been shown to induce liver cancer. The present risk assessment for PAHs is solely based on homocyclic PAHs. Yet, from the present review it becomes clear that this approach fails to protect against a vast number of heterocyclic compounds and biotransformation products that may exhibit stronger or other toxic effects than their homocyclic analogues. Therefore, incorporating the role of heterocyclic compounds and their metabolism appears to be a necessity for a reliable risk assessment for polycyclic aromatic compounds. In addition, reliable long-term protection against PAHs demands data on chronic toxicity, including teratogenicity, both for homocyclic as for heterocyclic compounds.
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PMID:Toxicity of azaarenes. 1177 50

The water sorption isotherm and the water vapor activity dependence of the enthalpy of water sorption Delta(sorp)Hdegrees of lysozyme have been measured at 25 degrees C. A thin film of lysozyme of mass 250 microg was exposed to H2O/N2 mixtures in a quartz crystal microbalance/heat conduction calorimeter (QCM/HCC). The QCM/HCC is a new gravimetric/calorimetric method that measures simultaneously and with high precision the mass change and the corresponding heat flow in a thin film exposed to a gas. Delta(sorp)Hdegrees for lysozyme agrees with previous determinations, although hysteresis effects are evident in the data. No van't Hoff analysis is necessary because sorption enthalpies are measured calorimetrically. The water vapor activity dependence of Delta(sorp)Hdegrees agrees with that measured previously by Bone. As the water content of the lysozyme film drops below 10 mass%, Delta(sorp)Hdegrees becomes more exothermic, indicating that water is being bound to the charged or highly polar groups of the solvent-accessible surface of lysozyme. The dynamics of water uptake and release from lysozyme thin films are much slower than in polymer films of comparable thickness. Because the QCM/HCC operates with sub-milligram samples, any protein is now amenable to study by this technique.
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PMID:Water sorption isotherms and enthalpies of water sorption by lysozyme using the quartz crystal microbalance/heat conduction calorimeter. 1182 17

Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.
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PMID:Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China. 1183 36

Hepatocellular carcinoma (HCC), on the rise in many countries, is of multifactorial etiology. Its etiological associations differ between populations at high and low risk. Africans and Chinese have the highest incidence of HCC, but other affected groups include African Americans, Japanese, and Native Americans. Chronic infections by hepatitis B and hepatitis C viruses are major risk factors worldwide, although mechanisms through which the infections cause liver cancer are yet to be explained. Other documented risk factors have been postulated and include dietary exposure, cigarette smoking, alcohol consumption, diabetes, oral infection, and oral contraceptive use. In addition, many naturally occurring and synthetic chemicals to which humans are exposed via accidental contamination of food or water are shown to induce liver cancer in experimental animals. Consequently, assessment of possible human liver cancer risk associated with such exposures is complex. Early diagnosis and transplantation are the best treatments presently, although transplantation is not widely available due to donor shortage. Every effort should be directed toward the prevention of HCC, through the treatment and prevention of hepatitis and oral infections, prevention of chronic hepatitis progressing to cirrhosis, and prevention of the cirrhotic liver from developing HCC through chemopreventive modalities. However, at present, very few such studies exist.
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PMID:Impact factors on development of cirrhosis and subsequent hepatocellular carcinoma. 1191 49

Chronic ingestion of arsenite-contaminated drinking water causes skin, bladder, and liver cancer. The mechanism of arsenite-induced carcinogenesis is unknown. Arsenite is known to disrupt mitosis and to delay transit through M phase in normal diploid fibroblasts. SV40-transformed human fibroblasts were observed to be hypersensitive to the cytotoxic and cytostatic effects of NaAsO(2) compared with normal diploid fibroblasts in concentration-response experiments. Five to 20 microM NaAsO(2) induced cytostasis in cycling normal diploid fibroblasts but not overt lethality in quiescent normal diploid fibroblasts. High concentrations of arsenite were overtly lethal in both cycling and quiescent cells. The IC50 for cycling SV40-transformed fibroblasts was 3.8 and 4.8 microM for the SV40-transformed lines GM4429 and GM0637, respectively, whereas, in cycling normal diploid fibroblasts (GM0024), the IC50 was 24.7 microM. Microscopic examination of NaAsO(2)-treated SV40-transformed fibroblasts suggested a concentration-dependent accumulation of cells in mitosis undergoing apoptosis. Treatment of SV40-transformed fibroblasts with 0-10 microM NaAsO(2) caused a concentration-dependent inhibition of cell proliferation, accumulation of cells having G2/M DNA contents, and increases in the mitotic index. Phase microscopy, annexin V binding, and electron microscopy demonstrated that arrested mitotic cells underwent apoptosis. These results indicate that SV40-transformation sensitizes cells to arsenite-induced mitotic arrest and induction of apoptosis in the mitotic cells.
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PMID:Arsenite disrupts mitosis and induces apoptosis in SV40-transformed human skin fibroblasts. 1196 75

In this paper, the technology for the preparation of plain carboxymethyl starch microsphere (CMS-MS) was optimized by the uniform design method with CMS-Na as carrier material and p-phthaloyl chloride as acrosslinker. The carboxymethyl starch microsphere loaded mitoxantrone (DHAQ-CMS-MS) was prepared by absorption method. Then, its morphology, size and size distribution, characteristics of drug loading, drug release in vitro, preparation for clinical application and its stability were studied. The pharmacokinetics of DHAQ-CMS-MS in rabbit was also studied. The results showed that the average diameter of the DHAQ-CMS-MS was 75.71 microns, drug loading was 13.21%, expansion ratio in water was 71.94%. The release of DHAQ in vitro from the microspheres was found to fit the model of single exponential function. The suspension prepared in this paper is not only convenient for clinical use, but also favorable for the improvement of the drug stability. The pharmacokinetic parameters obtained from the hepatic atery chemoembolization showed that the DHAQ-CMS-MS group, when compared with the solution group, exhibited a higher blood drug concentration in hepatic vein, its MRT was 1.96 times that of the solution group. As for the result of the peripheral vein, the MRT of the DHAQ-CMS-MS group was 1.95 times that of the solution group. This means that the drug when loaded in microsphere will be concentrated in its targeted site for a longer period, which is favorable for the treatment of hepatic cancer.
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PMID:[Study on the mitoxantrone carboxymethyl starch microspheres for hepatic artery chemoembolization]. 1201 32


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