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In this study, we attempted to elucidate the effects of ally isothiocyanates (AITC) on stress resistance. RGM1 cells, derived from the normal gastric mucosa of rats, were pretreated with AITC (0-30 μM) 24 hr or 48 hr prior to posttreatment with AITC (0 or 20 μM), or both. While approximately 90% of the vehicle-pretreated cells died by a posttreatment with AITC, pretreatments with AITC (10-30 μM), especially 24 hr prior and double pretreatments, exhibited striking cytoprotective effects. AITC, as a xenobiotic, increased the amounts of reactive oxygen species and insoluble proteins. On the other hand, double pretreatments with AITC markedly upregulated the mRNA expression levels of anti-oxidative, detoxification, and molecular chaperone genes for homeostasis. Interestingly, pretreatments with AITC (10 and 15 μM) significantly mitigated low-pH, but not high-pH, stress conditions, which may involve the activation of phosphoinositide 3-kinase and Na+/H+ exchanger. Taken together, we show here that multiple exposures to AITC can confer a stress resistance phenotype, including adaptation to acidic pH, by upregulating the expressions of self-defensive enzymes. Therefore, this study implies the importance of continuous ingestion of phytochemicals for efficiently increasing the stress resistance capacity against harmful chemicals.
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