Frontiers of Medicine

, Volume 12, Issue 2, pp 236–238 | Cite as

Carcinogens that induce the A:T > T:A nucleotide substitutions in the genome

  • Guangbiao Zhou
  • Xinchun Zhao


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.


genomic signature carcinogen aristolochic acid tobacco smoke vinyl chloride hepatocellular carcinoma 


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This work was supported by the National Natural Science Funds for Distinguished Young Scholar (No. 81425025).


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© Higher Education Press and Springer-Verlag GmbH Germany 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Membrane Biology, Institute of ZoologyChinese Academy of SciencesBeijingChina

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