title: Expression of stress-dependent genes in hepatocytes spheroids after cisplatin treatment.
abstract: Effects of cisplatin on the hepatic HepaRG cells cultured in spheroids were estimated using biochemical, cytofluorometric, and molecular methods. Hepatocyte viability and expression of mRNA of stress-dependent genes involved in the cell response to toxic agent cisplatin underwent time- and dose-dependent changes. Activation of oxidative stress was observed at the early stages of incubation (3 h) followed by induction of apoptosis after prolonging the incubation to 24 h. The prospects of using HepaRG cells cultured in spheroids for estimation of drug toxicity by variations in the expression of stress-dependent genes were demonstrated. An increase in expression of genes of GSR and HSPA1A proteins at the early stages of incubation with cisplatin can serve as a marker of the cytotoxic effects of cisplatin and other agents with similar mechanisms of action.
authors.affiliation: BioKlinikum Research and Development Centre, Moscow, Russia, a.rusanov@bioklinicum.ru.
authors.forename: A L
authors.initials: AL
authors.lastname: Rusanov
authors.forename: N V
authors.initials: NV
authors.lastname: Pul'kova
authors.forename: M G
authors.initials: MG
authors.lastname: Klonova
authors.forename: K A
authors.initials: KA
authors.lastname: Fomicheva
authors.forename: P M
authors.initials: PM
authors.lastname: Kozhin
authors.forename: M A
authors.initials: MA
authors.lastname: Sevast'yanova
authors.forename: M Yu
authors.initials: MY
authors.lastname: Shkurnikov
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002945:Cisplatin / Q000633:toxicity*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D017931:DNA Primers; D015870:Gene Expression; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D013315:Stress, Psychological
chemical_list: D017931:DNA Primers; D019392:Cytochrome P-450 CYP2E1; D051544:Cytochrome P-450 CYP3A; D002945:Cisplatin