title: Changes in hepatic cytosolic glutathione S-transferase activity and expression of its class-P during prenatal and postnatal period in rats treated with aflatoxin B1.
abstract: The effect of aflatoxin B1 (AFB1) on the expression of glutathione S-transferase-P (GST-P) which is the major isoform of GST in developmental stages has been investigated in rat liver during prenatal and postnatal stages. Following administration of AFB1 (0, 0.5, 1.0, 2.0, 3.0 or 4.0 mg/kg bw) injected I.P on day 8.5 of gestation the number of dead or reabsorbed fetuses and malformed embryos were recorded. Then the fetal livers were processed for measurement of total GST and GST-P activities, using 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid (ETA) as substrates respectively. RT-PCR using rat GST-P specific primers was performed on mRNA extracted from livers. Besides, the effects of AFB1 on hepatic GST and GST-P were assessed in groups of suckling rats directly injected with the toxin. The results show that a single dose of AFB1 (1.0 or 2.0 mg/kg bw) caused approximately 50-60% depletion in fetal liver GST towards CDNB. Postnatal experiments revealed that liver GST (using CDNB as substrate) was significantly induced (approximately 40%) in suckling rats injected with a single dose of AFB1 (3.0 mg AFB1/kg) 24 h before killing. Liver GST-P expression was unaffected due to AFB1 exposures of rats before and after the birth. This finding was substantiated by western blotting and RT-PCR techniques. These data suggest that AFB1-related induction in rat liver total GST after birth may be implicated in protective mechanisms against AFB1. In contrast, inhibition of this enzyme in fetal liver following placental transfer of the carcinogen may explain high susceptibility of fetal cells to trans-plancental aflatoxins. Furthermore, lack of influence of AFB1 on GST-P expression in developmental stages can role out the involvement of this class of GST in AFB1 biotransformation.
authors.affiliation: Department of Biochemistry Faculty of Medical Science, Tarbiat Modarres University, P.O. Box 14115-331, Tehran, Iran.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Fatemi
authors.forename: Abdolamir
authors.initials: A
authors.lastname: Allameh
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Dadkhah
authors.forename: Mehdi
authors.initials: M
authors.lastname: Forouzandeh
authors.forename: Somayeh
authors.initials: S
authors.lastname: Kazemnejad
authors.forename: Roya
authors.initials: R
authors.lastname: Sharifi
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D000833:Animals, Suckling; D015153:Blotting, Western; D003600:Cytosol / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D018811:Maternal Exposure; D011042:Poisons / Q000633:toxicity*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011042:Poisons; D012333:RNA, Messenger; D016604:Aflatoxin B1; D005982:Glutathione Transferase