Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Arsenite-induced cancer is known to be development after a latent period, even after the exposure is discontinued. Previously, we have shown that arsenite exposure induces premature senescence and senescence-associated secretory phenotype (SASP) factors in hepatocytes. However, it is unclear whether arsenite exposure-induced premature senescence and SASP factors are maintained even after cessation of arsenite exposure. In this study, we examined whether the arsenite exposure-induced premature senescence and SASP factors in hepatocytes persist after cessation of arsenite exposure.
As a result, senescent features such as morphological changes (enlarged and flatten) and changes of mRNA levels of senescence markers (P21 induction and LAMINB1 reduction) were maintained after 100 hours from cessation of 5 μM sodium arsenite exposure for 72 hours in Huh-7 cells. At that time, mRNA levels of SASP factors (MMP1, MMP3, MMP10, GDF15, PAI-1 and IL-6) were also significantly increased. We further confirmed that senescent cells still exist 7 days after cessation of the exposure by performing SA-β-gal staining. Furthermore, almost SASP factors that were upregulated by arsenite exposure in hepatocytes showed a positive correlation between increased expression and poor prognosis in human hepatocellular carcinoma by analyzing TCGA database.
These results showed that arsenite exposure-induced premature senescence followed by SASP induction is maintained in hepatocytes even after cessation of arsenite exposure and the SASP factors can be involved in progression of cancer.
