title: Imprinting of cerebral and hepatic cytochrome p450s in rat offsprings exposed prenatally to low doses of cypermethrin.
abstract: Oral administration of low doses (1.25 or 2.5 or 5 mg/kg) corresponding to 1/200th or 1/100th or 1/50th of LD50 of cypermethrin, a synthetic type II pyrethroid, to pregnant Wistar rats from gestation day 5 to 21 produced a dose-dependent increase in the expression of xenobiotic metabolizing cytochrome P450 (CYP) 1A-, 2B- and 2E1 in the brain and liver of offsprings postnatally at 3 weeks that persisted up to 12 weeks. This persistent increase in CYPs was associated with alterations in circulating concentrations of testosterone, luteinizing hormone and follicle stimulating hormone, spontaneous locomotor activity and accumulation of cypermethrin in the brain of exposed offsprings. Rechallenge of exposed offsprings at adulthood (12 weeks old) with cypermethrin (p.o., 10 mg/kg × 6 days) led to a much higher increase in the expression of CYPs in the exposed offsprings when compared to the control offsprings treated with cypermethrin. Further, bioinformatic analysis demonstrating absence of specific short interspersed elements in CYPs suggests that persistence in the increase in CYPs in exposed offsprings could be attributed to the imprinting of the cerebral and hepatic CYPs following prenatal exposure to low doses of cypermethrin. This imprinting could be of toxicological relevance as it may modify the response of drugs or environmental exposures in exposed offsprings particularly for those chemicals which require CYP-mediated metabolism to produce their beneficial or toxic effects.
authors: Developmental Toxicology Division, Indian Institute of Toxicology Research (IITR), CSIR, PO Box 80, M.G. Marg, Lucknow, 226 001, Uttar Pradesh, India. anshuman321_80@hotmail.com
authors: Anshuman
authors: A
authors: Singh
authors: Sanjay
authors: S
authors: Yadav
authors: Vikas
authors: V
authors: Srivastava
authors: Rakesh
authors: R
authors: Kumar
authors: Dhirendra
authors: D
authors: Singh
authors: Rao
authors: R
authors: Sethumadhavan
authors: Devendra
authors: D
authors: Parmar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018392:Genomic Imprinting / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008861:Microsomes / Q000201:enzymology; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D011722:Pyrethrins / Q000378:metabolism / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D006728:Hormones; D011722:Pyrethrins; D012333:RNA, Messenger; C017160:cypermethrin; D003577:Cytochrome P-450 Enzyme System