Acrylamide induces cellular senescence in macrophage through ROS‐MAPK signaling pathway

Acrylamide (ACR) has been known to induce versatile adverse effects such as genotoxic and immunotoxic effects. Cellular senescence is the state of stable cell cycle arrest provoked by a variety of potentially oncogenic stimuli, such as telomere shortening, DNA damage or activation of certain oncogenes. We examined the effect of ACR on the cellular senescence in macrophage. Our results showed that ACR reduced the cell proliferation in a concentration‐ and time‐dependent manner, along with flattened and enlarged morphological changes. There was an increased level of beta‐galactosidase activity at pH6 with increasing treatment time of ACR for 1, 3 and 5 days, respectively. Cells treated with ACR showed a dose‐dependent increase in G0/G1 phase arrest. Western blot analysis demonstrated that the levels of p53 and p21 were increased in ACR‐treated with macrophage. In addition, Cdk2 and Cdk4 levels were decreased, which correlated with G0/G1 phase arrest. Furthermore, the induction of senescence in ACR treated macrophage was initiated by reactive oxygen species (ROS) production, leading to the activation of the p38 MAPK and JNK pathway. Incubation of macrophage with N‐acetylcysteine, an inhibitor of ROS, decreased p38 MAPK and JNK activation and attenuated senescence induction by ACR. Taken together, the present data suggest that ACR treatment induces cellular senescence through ROS‐MAPK pathway.