Modulation in the developmental expression profile of Sp1 subsequent to transplacental exposure of fetal rats to desorbed benzo[a]pyrene following maternal inhalation.
Any alteration of the critical sequence of genes that are required to coordinate the differentiation of cells, the promotion of migration, dendritic arborization, synapse formation, and myelination in the developing nervous system would be expected to have deleterious consequences. The focus of this article is a molecular evaluation of the neurotoxicological effects that result subsequent to the transplacental exposure of fetal rats to desorbed benzo(a)pyrene (BaP) following maternal inhalation. A state-of-the-art, newly designed, fabricated, and tested model aerosol generation system was utilized in these studies. Timed-pregnant Sprague Dawley rats were exposed for 4 h on gestation day 15 of a 21-day gestation period to an acute dose of BaP:carbon black aerosol (100 microg/m(3)). Controls received carbon black only. Nominal and chamber concentrations of the particulate aerosol were determined gravimetrically with a seven-stage cascade impactor. The aerosol exhibited a trimodal distribution with 95% cumulative mass less than 15.85 microm, 90% cumulative mass less than 10 microm, 67. 5% cumulative mass less than 2.5 microm and 66.2% cumulative mass less than 1.0 microm. Time-course bioavailability results indicated that greater than 95% of the parent compound is cleared from blood 240 min postexposure. An Sp1 transcription factor consensus sequence was examined by electrophoretic mobility shift analysis of nuclear extracts from various brain regions of resulting pups on postnatal days 3, 5, 7, 10, and 15. It revealed perturbations in the developmental expression profile of Sp1 abundance as a result of nose-only particulate aerosol exposure to the timed-pregnant dam. The data obtained on the temporal and spatial regulation of gene expression in the brain indicate that (1) Sp1 DNA-binding is developmentally regulated and expressed very highly in actively developing brain regions, and (2) a consequence of the transplacental deposition of desorbed BaP to the fetus is in utero neurotoxicity.
Hood
D B
DB
Department of Pharmacology, Meharry Medical College, 1005 D. B. Todd Blvd., Nashville, TN 37208, USA. DbhTox@AOL.com.
Nayyar
T
T
Ramesh
A
A
Greenwood
M
M
Inyang
F
F
D000280:Administration, Inhalation; D000336:Aerosols; D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000378:metabolism; D002244:Carbon / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D019570:Inhalation Exposure; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D010316:Particle Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016329:Sp1 Transcription Factor / Q000187:drug effects* / Q000378:metabolism
D000336:Aerosols; D000393:Air Pollutants; D016329:Sp1 Transcription Factor; D001564:Benzo(a)pyrene; D002244:Carbon