Abstract Objective: Present study investigated the effect of tobacco-specific carcinogen, nicotine-derived nitrosamine ketone (NNK), on the expression of cellular stress response genes in lung tissue of Wistar rats. Moreover, the effect of exercise training on alterations of these genes in exposed rats was investigated. Materials and Methods: A total of 30 healthy Wistar rats were obtained and divided into the following group: (1) Control (CON), (2) NNK exposure (NNK, once a week / 12.5 mg per kg body mass for 12 weeks), and NNK + swimming training (NNK+ST, received NNK exposure + 25-60 min of aerobic swimming training / 5 days per week for 12 weeks). The mRNA expression level of nuclear factor kappa-B (NF-κB), forkhead box protein O3 (FOXO3), and Sirtuin-1 (Sirt-1) were determined in lung tissue by the quantitative real-time PCR. Results: The NNK exposure resulted in a significant reduction in mRNA expression of the NF-κB and FOXO3 (P=0.0001 and P=0.005, respectively), as well as a significant increment in mRNA expression of Sirt-1 (P=0.001) comparing to the CON group. Moreover, the ST in rats under NNK treatment led to a significant reduction in mRNA expression of NF-κB (P=0.0001), but it did not have any significant effect on mRNA expression of FOXO3 and Sirt-1 (P>0.05) comparing to the NNK group. Conclusion: These findings indicate that NNK exposure can lead to adverse alterations in the expression of cellular stress response genes in the lung tissue of Wistar rats and exercise training may not have any favorable effect on the expression of these genes in rats under NNK treatment.
