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    Home > Medical News > Medical Science News > Horse bell acid is just one of the "suspects" of liver cancer

    Horse bell acid is just one of the "suspects" of liver cancer

    • Last Update: 2020-12-20
    • Source: Internet
    • Author: User
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    , alvin W. T. Ng et al. reported in 2017 that horse bell acid is the cause of liver cancer. Zhou Guangxuan and Zhao Xinchun, national key laboratories of membrane biology at the Institute of Zoology of the Chinese Academy of Sciences, published "Madu suzuki is only one of the "suspects" of liver cancer in
    (headline:
    ), arguing that other carcinogens and even drugs can cause this genomic mutation, so Madu suzuki is only one of the "suspects→ of liver cancer, and assessing the history of exposure to carcinogens in patients is the key to identifying the culprits for the A→T mutation. See below for details.
    Recently, Ng et al.
    sequenced a sample of 98 patients with hepatocellular carcinoma from Taiwan, China, and found that 78 percent of the patients had a nucleotide replacement (A) mutation of adenine (T) in their genomes, which they considered a characteristic mutation in exposure to horse's belling acid→. They also analyzed test data from samples of 1,400 patients with hepatocellular carcinoma from different regions and found that patients with hepatocellular carcinoma in Chinese mainland, Southeast Asia, South Korea, Japan, North America and Europe also had A→T nucleotide replacements, between 47% and 1.7%. As a result, they concluded that marmaid acid causes mutations in genomic A→T nucleotides, a major cause of hepatocellular carcinoma. Unfortunately, they did not assess the patient's history of exposure to horse-bell acid and the exposure dose.In the 1970s, horse bell acid was thought to be a nephrotoxic and carcinogenic substance for two reasons: horse bell acid in wheat flour mixed with the seeds of the horse's bell plant iron lotus was thought to be associated with more Balkan endexual nephropathy is associated with people in rural areas along the Nau River, and plant weight-loss pills containing horse bell acid used in a clinic in Brussels, Belgium, are closely related to renal toxicity (later known as horse bell acid nephropathy) and epidertic cell carcinoma on the urethra
    . However, only 2 to 5 per cent of the population in the Endemic Kidney Disease Epidemic Zone in the Balkans became ill, and only 10 to 20 per cent of patients who took plant weight-loss pills at the Brussels clinic became
    . In addition, Germany has been using marmaline as an immunomodulating drug for 25 years, treating thousands of patients, but no cases of kidney disease or urethra tumors have been reported
    .
    can cause renal toxicity in experimental animals and cause tumors in rats to
    . Horse bell acid is thought to be the culprit for local kidney disease in the Balkans, based on the fact that horse's bell acid exposure induces tumors and causes the c-Ha-ras, c-Ki-ras and N-ras genes to produce A→T nucleotide replacement
    , while the TP53 gene in endexual nephropathy and upper urethra cell carcinoma patients also has A→T nucleotide replacement
    . The whole genome and whole exon group sequencing samples of skin cell carcinoma associated with horse's bell acid were sequenced, and A→T nucleotide replacement was found to have occurred in other genes
    .Compared to normal tissue samples, the cancer genome usually has six types of nucleotide replacement or mutation: ostrich (G) becomes adenine (G→A), ostrich becomes thymus (G→T), and ostrich becomes cytosine (C; G→C), adenine to ostrich (A→G), adenine to thymus (A→T), and adenine to cytosine (A→C). Some environmental factors can cause characteristic changes (i.e. imprints) in the human genome, such as polycyclic aromatic hydrocarbons produced by smoking or present in fine air particle pollutants that induce mutations in the genome of G→T
    . It is important to note that a type of nucleotide change can be a genomic imprint of multiple carcinogens, and multiple carcinogens can cause the same type of genomic imprinting. Horse bell acid can cause the genomes of cells, animals, and patients to produce A→T replacements, while other carcinogens can also cause such genomic imprinting (Table 1). For example, tobacco carcinogens 4-aminobenzene and 1,3-butylene
    can cause A→T replacement of H-Ras and HPRT
    . Vinyl chloride
    and its active metabolite vinyl oxide
    have been shown to induce the A→T nucleotide replacement of the TP53 gene
    . The cancer drugs melphalan and chlorambucil also cause the TP53, N-RAS and HPRT genes to produce A→T replacement
    .。 Han Zeguang and others reported in 2012 that the genomes Chinese mainland patients with hepatocellular carcinoma had the characteristics of A→T nucleotide replacement
    . Horse bell acid causes changes in the genome A→T nucleotides, however, other carcinogens can also cause such mutations. Because smoking poses a serious threat to public health, vinyl chloride is widely distributed around the world and is a common source of air
    . Therefore, the evaluation of the history of exposure to carcinogens in patients is the key to → cause the A-T mutation. Clearly, Ng et al.'s findings are neither new
    nor persuasive due to a lack of assessment of a patient's exposure history.。 1. Ng AWT, Poon SL, Huang MN, et al. Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia. Sci Transl Med. 2017; 9(412):pii: eaan6446.
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    4. de Jonge H, Vanrenterghem Y. Aristolochic acid: the common culprit of Chinese herbs nephropathy and Balkan endemic nephropathy. Nephrol Dial Transplant. 2008; 23:39-41.
    5. Schmeiser HH, Janssen JWG, Lyons J, et al. Aristolochic Acid Activates ras Genes in Rat Tumors at Deoxyadenosine Residues. Cancer Res. 1990; 50(17):5464-5469.
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    9. Manjanatha MG. H- and K-ras mutational profiles in chemically induced liver tumors from B6C3F1 and CD-1 mice. Toxicol Environ Health. 1996; 47(2):195-208.
    10. Ma H, Wood TG, Ammenheuser MM, Rosenblatt JI, Ward JB, Jr. Molecular analysis of hprt mutant lymphocytes from 1, 3-butadiene-exposed workers. Environ Mol Mutagen. 2000; 36(1):59-71.
    11. Wagoner JK. Toxicity of vinyl chloride and poly(vinyl chloride): a critical review. Environ Health Perspect. 1983; 52:61-66.
    12. Hollstein M, Marion MJ, Lehman T, et al. p53 mutations at A:T base pairs in angiosarcomas of vinyl chloride-exposed factory workers. Carcinogenesis. 1994; 15(1):1-3.
    13. Wang P, Bennett RAO, Povirk LF. Melphalan-induced Mutagenesis in an SV40-based Shuttle Vector: Predominance of A · T→T · A Transversions. Cancer Res. 1990; 50(23):7527-7531.
    14. Povirk LF, Shuker DE. DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res. 1994; 318(3):205-226.
    15. Hoang ML, Chen CH, Sidorenko VS, et al. Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing. Sci Transl Med. 2013; 5(197):197ra102.
    16. Houle CD, Ton T-VT, Clayton N, Huff J, Hong H-HL, Sills RC. Frequent p53 and H-ras Mutations in Benzene- and Ethylene Oxide-Induced Mammary Gland Carcinomas from B6C3F1 Mice. Toxicol Pathol. 2006; 34(6):752-762.
    17. Poon SL, Pang S-T, McPherson JR, et al. Genome-Wide Mutational Signatures of Aristolochic Acid and Its Application as a Screening Tool. Sci Transl Med. 2013; 5(197):197ra101-197ra101.
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