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Researchers Uncover Mechanism of Tobacco Carcinogen. 

A group of investigators has discovered that nicotine-derived nitrosamine ketone (NNK), a tobacco carcinogen, not only causes DNA and genetic alteration but also induces epigenetic alterations in the process of cancer formation, inhibiting tumor suppressor genes.

The findings appear in a paper titled "The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation and tumor suppressor gene hypermethylation in mice and lung cancer patients," published in The Journal of Clinical Investigation. The research team was led by Yi-Ching Wang, Ph.D., department of pharmacology, National Cheng Kung University.

DNA methyltransferase 1 (DNMT1) catalyzes DNA methylation and is overexpressed in many human diseases including cancer. The tobacco-specific carcinogen NNK also induces DNA methylation. The role of DNMT1-mediated methylation in tobacco carcinogenesis, however, remains unclear.

To better understand this mechanism, the researchers used human and mouse lung cancer samples and cell lines to determine how NNK induced DNMT1 expression and activity and triggered the inhibition of tumor suppressor genes.

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