Carcinogenicity of acrolein, crotonaldehyde, and arecoline

Acrolein alters cell proliferation, cell death, or nutrient supply, inhibiting tumour suppressor genes and activating proto-oncogenes in cultured human and rodent cells, and inducing hyperplasia and metaplasia in the rodent respiratory system.2,3 Overall, there is “strong” evidence that acrolein exhibits multiple key characteristics of carcinogens, primarily from studies with human primary cells and studies in experimental systems, supported by studies in humans on DNA adducts. An electrophilic α,β-unsaturated aldehyde (enal), crotonaldehyde forms cyclic adducts in DNA as well as DNA interstrand and DNA–protein cross-links. α-Methyl-γ-hydroxy-1,N2-propanodeoxyguanosine has been detected in human saliva, urine, blood, mammary tissue, oral (gingival) tissue, liver, and placenta.4,5 Adduct levels were significantly elevated in tobacco smokers.4 Crotonaldehyde-derived DNA adducts have also been detected in human cells in vitro and in rodents. Crotonaldehyde is genotoxic, exhibiting clastogenicity in human primary cells and human cell lines,8 dominant lethality and chromosomal aberrations in rodents, and gene mutations in cultured rodent cells, Drosophila melanogaster, Salmonella typhimurium, and plasmid systems.