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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2018, Vol. 12 Issue (2) : 236-238    https://doi.org/10.1007/s11684-017-0611-y
COMMENTARY |
Carcinogens that induce the A:T>T:A nucleotide substitutions in the genome
Guangbiao Zhou(), Xinchun Zhao
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
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Abstract

Recently, Ng et al. reported that the A:T>T:A substitutions, proposed to be a signature of aristolochic acid (AA) exposure, were detected in 76/98 (78%) of patients with hepatocellular carcinoma (HCC) from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients’ exposure history is the key to determine the “culprit” of the A:T>T:A mutations. Apparently, without estimation of the patients’ exposure history, the conclusion of Ng et al. is unpersuasive and misleading.

Keywords genomic signature      carcinogen      aristolochic acid      tobacco smoke      vinyl chloride      hepatocellular carcinoma     
Corresponding Authors: Guangbiao Zhou   
Just Accepted Date: 08 November 2017   Online First Date: 01 December 2017    Issue Date: 02 April 2018
 Cite this article:   
Guangbiao Zhou,Xinchun Zhao. Carcinogens that induce the A:T>T:A nucleotide substitutions in the genome[J]. Front. Med., 2018, 12(2): 236-238.
 URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0611-y
http://academic.hep.com.cn/fmd/EN/Y2018/V12/I2/236
Agents/carcinogens Sites of related cancers Affected genes References
4-aminobiphenyl Liver, bladder, urinary H-Ras [9]
1,3-Butadiene Bone marrow HPRT [10]
AA Upper urothelial cancer RAS, TP53, exosome wide [1,5,6,15,16]
Ethylene oxide Stomach, marrow H-Ras [17]
Melphalan and chlorambucil Breast, ovarian, marrow TP53, N-RAS, Hprt [13,14]
Vinyl chloride Liver TP53 [12]
Tab.1  Carcinogens causing the A:T>T:A nucleotide substitutions
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https://doi.org/10.1126/scitranslmed.aan6446 pmid: 29046434
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https://doi.org/10.1007/s00204-016-1819-3 pmid: 27538407
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https://doi.org/10.1093/ndt/gfm667 pmid: 17913731
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pmid: 2201437
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https://doi.org/10.1073/pnas.0701248104 pmid: 17620607
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https://doi.org/10.1016/j.mrrev.2016.03.004 pmid: 27234561
9 Manjanatha MG, Li EE, Fu PP, Heflich RH. H- and K-ras mutational profiles in chemically induced liver tumors from B6C3F1 and CD-1 mice. J Toxicol Environ Health 1996; 47(2): 195–208
https://doi.org/10.1080/009841096161898 pmid: 8598575
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
https://doi.org/10.1002/1098-2280(2000)36:1<59::AID-EM9>3.0.CO;2-# pmid: 10918361
11 Wagoner JK. Toxicity of vinyl chloride and poly(vinyl chloride): a critical review. Environ Health Perspect 1983; 52:61–66
pmid: 6360677
12 Hollstein M, Marion MJ, Lehman T, Welsh J, Harris CC, Martel-Planche G, Kusters I, Montesano R. p53 mutations at A:T base pairs in angiosarcomas of vinyl chloride-exposed factory workers. Carcinogenesis 1994; 15(1): 1–3
https://doi.org/10.1093/carcin/15.1.1 pmid: 8293534
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
pmid: 2174727
14 Povirk LF, Shuker DE. DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res 1994; 318(3): 205–226
https://doi.org/10.1016/0165-1110(94)90015-9 pmid: 7527485
15 Hoang ML, Chen CH, Sidorenko VS, He J, Dickman KG, Yun BH, Moriya M, Niknafs N, Douville C, Karchin R, Turesky RJ, Pu YS, Vogelstein B, Papadopoulos N, Grollman AP, Kinzler KW, Rosenquist TA. Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing. Sci Transl Med 2013;5(197):197ra02
https://doi.org/DOI: 10.1126/scitranslmed.3006200 pmid: 23926200
16 Poon SL, Pang ST, McPherson JR, Yu W, Huang KK, Guan P, Weng WH, Siew EY, Liu Y, Heng HL, Chong SC, Gan A, Tay ST, Lim WK, Cutcutache I, Huang D, Ler LD, Nairismägi ML, Lee MH, Chang YH,Yu KJ, Chan-On W, Li BK, Yuan YF, Qian CN, Ng KF, Wu CF, Hsu CL, Bunte RM, Stratton MR, Futreal PA, Sung WK, Chuang CK, Ong CK, Rozen SG,Tan P, Teh BT. Genome-wide mutational signatures of aristolochic acid and its application as a screening tool. Sci Transl Med 2013; 5(197):197ra101
https://doi.org/10.1126/scitranslmed.3006086 pmid: 23926199
17 Houle CD, Ton TVT, Clayton N, Huff J, Hong HHL, 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
https://doi.org/10.1080/01926230600935912 pmid: 17162533
18 Huang J, Deng Q, Wang Q, Li KY, Dai JH, Li N, Zhu ZD, Zhou B, Liu XY, Liu RF, Fei QL, Chen H, Cai B, Zhou B, Xiao HS, Qin LX, Han ZG. Exome sequencing of hepatitis B virus-associated hepatoccelular carcinoma. Nat Genet 2012; 44(10): 1117–1121
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