(W1030-05-29) Cinnamaldehyde DNA Adducts are Mutagenic and Block Replication

Purpose: Cinnamaldehyde(CA) is a chemical from spice cinnamon, which is the source of cinnamon odor. In electronic cigarettes industry, CA is widely used as an ingredient of e-cigarette oil. The safety of using CA in e-cigarette has never been investigated because CA is traditionally considered as a safe food ingredient. The α, β-unsaturated aldehyde structure of CA could form adduct with Guanine, which could block DNA replication, affects genome integrity and cell metabolism. Our aim is to identify the structure of the adduct formed by CA with DNA base guanine, and determine the mutagenicity .

Methods: 2’-Deoxyguanosine nucleoside was reacted with CA to generate cinnamaldehyde-induced 2’-dG adduct, the adduct was purified by HPLC and characterized by NMR. In addition, Cinnamaldehyde was incubated with short oligo which contains only one guanine. The oligo-CA adduct was purified by HPLC and characterized by LC-MS. The toxicity and mutagenicity of CA-adduct are determined with CRAB (competitive replication and adduct bypass) and REAP (restriction endonuclease and post-labeling) assays.

Results: The NMR shows the CA can form cyclic adduct with guanine under physiological condition and the adducts are two consist of two diastereomers. The CA-adduct can block DNA polymerase and cause mutation.

Conclusion: CA can form bulky adducts with guanine and potentially cause the e-cigarette related lung diseases. The use of CA in e-cigarette needs further safety assessment.

References: King, A. A. et al. Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair. Mutat. Res. Mol. Mech. Mutagen. 616, 60–69 (2007).

Kiwamoto, R., Ploeg, D., Rietjens, I. M. C. M. & Punt, A. Dose-dependent DNA adduct formation by cinnamaldehyde and other food-borne α,β-unsaturated aldehydes predicted by physiologically based in silico modelling. Toxicol. In Vitro 31, 114–125 (2016).