Increased mortality risk for cancers of the kidney and other urinary organs among Chinese herbalists.
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BACKGROUND: A national survey in Taiwan has shown that Chinese herbal therapy increases the risk of chronic kidney disease. However, it is unknown whether herbal therapy will increase the risk of urological cancers. The purpose of this study was to determine whether Chinese herbalists are at higher risk for urological cancers. METHODS: We studied all Chinese herbalists in Taiwan that were registered in the Chinese Herbalist Labor Union between 1985 and 2000. We retrospectively followed their survival status and causes of death using the National Mortality Registry Database from 1985 to 2004. Standardized mortality ratios (SMRs) for urological cancers in herbalists were calculated and compared with those of the general population of Taiwan. RESULTS: A total of 6548 Chinese herbalists were enrolled and 88,289 person-years were accrued during the observation period. After adjustment for age and sex, the SMR for urological cancers was significantly higher for Chinese herbalists than for the general population (SMR = 3.10; 95% CI: 1.41-5.87). When further stratified by location, the SMR for kidney cancer and other urinary organ cancers (SMR = 3.81; 95% CI: 1.39-8.28) except bladder cancer (SMR = 2.26; 95% CI: 0.47-6.59) were significantly higher for the Chinese herbalists. The SMR for chronic and unspecified nephritis, renal failure, and renal sclerosis were also significantly higher for herbalists (SMR = 2.40; 95% CI: 1.40-3.84). CONCLUSIONS: Chinese herbalists have a significantly higher risk for urological cancers. This increased risk among herbalists highlights the urgent need for safety assessments of Chinese herbs. (+info)
The role of biotransformation enzymes in the development of renal injury and urothelial cancer caused by aristolochic acid: urgent questions and difficult answers.
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BACKGROUND: Ingestion of aristolochic acid (AA) is associated with the development of aristolochic acid nephropathy (AAN), which is characterized by chronic renal failure, tubulointerstitial fibrosis and urothelial cancer. AA may also cause another type of kidney fibrosis with malignant transformation of the urothelium, called Balkan Endemic Nephropathy (BEN). The compound predominantly responsible for the nephropathy and urothelial cancer of AA, is aristolochic acid I (AAI) which is a genotoxic mutagen after metabolic activation The activation pathway involves reduction of the nitro group to a cyclic N-acylnitrenium ion that can form covalent DNA adducts. These specific DNA adducts have been detected in experimental animals exposed to AAI, and in urothelial tissues from AAN patients. In rodent tumours induced by AAI, 7-(deoxyadenosin-N(6)-yl)aristolactam I was the most abundant DNA adduct formed and associated with activation of ras oncogenes through a characteristic transversion mutation. Such A:T-->T:A mutations have been identified in TP53 of urothelial tumour DNA of an AAN patient and in several patients suffering from BEN along with specific AA-DNA adducts. Understanding which enzymes are involved in AAI activation to species forming DNA adducts and/or detoxification to its O-demethylated metabolite aristolochic acid Ia (AAIa) is important in order to assess susceptibility to this carcinogen. METHODS AND RESULTS: A literature search. CONCLUSIONS: The most important human enzymes activating AAI by simple nitroreduction in vitro are hepatic and renal cytosolic NAD(P)H:quinone oxidoreductase, hepatic microsomal cytochrome P450 (CYP) 1A2 and renal microsomal NADPH:CYP reductase as well as cyclooxygenase which is highly expressed in urothelial tissue. However, the contribution of most of these enzymes to the development of AAN and BEN diseases is still unclear. Hepatic CYP enzymes were found to detoxify AAI to AAIa in mice, and thereby protect the kidney from injury. CYP enzymes of the 1A subfamily seem to play a major role in this process in mouse liver. Likewise, among human CYP enzymes, CYP1A1 and 1A2 were found to be the most efficient enzymes participating in AAI oxidation to AAIa in vitro. Nevertheless, which CYPs are the most important in this process in both animal models and in humans have not been entirely resolved as yet. In addition, the relative contribution of enzymes found to activate AAI to species responsible for induction of urothelial cancer in humans remains still to be resolved. (+info)
p53 mutations as fingerprints for aristolochic acid: an environmental carcinogen in endemic (Balkan) nephropathy.
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Determination of the volatile and semi-volatile secondary metabolites, and aristolochic acids in Aristolochia ringens Vahl.
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Volatile and semi-volatile secondary metabolites, as well as aristolochic acids (AA), present in leaves, stems, and flowers of Aristolochia ringens were determined by gas chromatography (GC)-mass spectrometry (MS) and high-performance liquid chromatography (HPLC) methods, respectively. Metabolite isolation was performed using different extraction techniques: microwave-assisted hydrodistillation (MWHD), supercritical fluid extraction, and headspace solid-phase microextraction (HS-SPME). The chemical composition of the extracts and oils was established by GC-MS. The determinations of AAI and AAII were conducted by methanolic extraction of different plant parts followed by HPLC analysis. Essential oil yields from leaves and stems were 0.008 +/- 0.0022% and 0.047 +/- 0.0026%, respectively. Aristolochia ringens flowers did not yield essential oil under MWHD. Sesquiterpene hydrocarbons (66%) were the main compounds in the essential oil isolated from leaves whereas monoterpene hydrocarbons (73%) predominated in the stems essential oil. Yields of extracts isolated by SFE from leaves, stems, and flowers were 4 +/- 1.8%, 1.2 +/- 0.25%, and 4 +/- 1.8%, respectively. In vivo HS-SPME of flowers isolated compounds with known unpleasant smells such as volatile aldehydes and short-chain carboxylic acids. HPLC analysis detected the presence of AAII in the flowers of Aristolochia ringens at a concentration of 610 +/- 47 mg/kg of dried flower. (+info)
DNA adducts of aristolochic acid II: total synthesis and site-specific mutagenesis studies in mammalian cells.
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