Transcriptional induction of CYP3A4 by o,p'-DDT in HepG2 cells.
Technical grade DDT, a commonly used pesticide, contains 20% of the o,p'-DDT isomer. It alters the activity of hepatic mixed function oxidase and induces expression of cytochrome P450 such as 3A subfamilies. In the present study, we analyzed the effects of o,p'-DDT on CYP3A4 gene expression in HepG2 cells. Treatment with o,p'-DDT dose-dependently increased levels of CYP3A4 mRNA and the immunoreactive protein, by 13- and 3.8-fold, respectively, relative to untreated cultures. Treatment with actinomycin D blocked the o,p'-DDT-induced increase in CYP3A4 mRNA levels. These findings demonstrate that this insecticide is able to induce CYP3A4 transcription and may play an important role in the modulation of endogenous hormones and xenobiotic metabolism.
Medina-Díaz
Irma M
IM
Toxicology Section, CINVESTAV-IPN, PO Box 14-740, Mexico, D.F. 07000, Mexico.
Elizondo
G
G
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003634:DDT / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004968:Estrogens, Non-Steroidal; D003577:Cytochrome P-450 Enzyme System; D003634:DDT; C016340:o,p'-DDT; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human