Figure 1.

Diagrammatic models summarizing simplified molecular mechanisms of genotoxic and non-genotoxic modes of action in carcinogenesis by cigarette smoke. (a) Nitrosamines and PAHs are carcinogens, inducing genotoxic effects leading to cancer initiation. (b) Non-genotoxic (epigenic) effects of cigarette smoke components (nicotine, nitrosamines, and PAHs) in cancer promotion and progression. Activation of nAChR, β-AR, or AhR, followed by neurotransmitters release, activation of signaling pathways (PKA, 5-LOX, Stat3 and PPARβ/δ), and increased the expression of transcriptional factors (JUN, FOS, MYC, and CREB) regulate cancer promotion by cigarette smoke. PKC, PI3K/AKT, ERK, and COX-2 signaling pathways downstream of receptors play important roles in both promotion and progression stages. p38, Src, VEGF, and NO releasing involve in enhancement of cancer progression by cigarette smoke.