(a) Overview of in vitro experiments using human lung cancer cell lines (H460 and H510) treated with THS (1:80). The culture medium was replaced every three days with fresh THS or control supplemented culture media. (b) Heatmap of differentially expressed genes in H510 cells collected at day 12 (see Figure 2a). Genes regulated by ATF4, TP53, and NUPR1 are indicated in blue bars underneath the heatmap. (c) Overlap of genes differentially expressed in H510 cells and a human smoking signature published previously [30]. (d) Canonical pathways significantly enriched in response to THS exposure in H510 cells. (e) Gene interaction network in response to THS exposure enriched for p53 and ER stress signaling. Genes up-regulated after THS exposure are highlighted in red; down-regulated genes are highlighted in green. Genes that are also deregulated in the published human smoking signature are further highlighted in purple.