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Carcinogens that induce the A:T>T:A nucleotide substitutions in the genome
Guangbiao Zhou, Xinchun Zhao
Frontiers of Medicine 2018, Volume 12, Issue 2, Pages 236-238 doi: 10.1007/s11684-017-0611-y
Recently, Ng . 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 is unpersuasive and misleading.
Keywords： genomic signature carcinogen aristolochic acid tobacco smoke vinyl chloride hepatocellular carcinoma
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