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 coord inate the differentiation of cells, the promotion of migration, dendritic a rborization, synapse formation, and myelination in the developing nervous s ystem would be expected to have deleterious consequences. The focus of this article is a molecular evaluation of the neurotoxicological effects that r esult subsequent to the transplacental exposure of fetal rats to desorbed b enzo(a)pyrene (BaP) following maternal inhalation. A state-of-the-art, newl y designed, fabricated, and tested model aerosol generation system was util ized 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 Ba P:carbon black aerosol (100 mu g/m(3)). Controls received carbon black only . Nominal and chamber concentrations of the particulate aerosol were determ ined gravimetrically with a seven-stage cascade impactor. The aerosol exhib ited a trimodal distribution with 95% cumulative mass less than 15.85 mu m, 90% cumulative mass less than 10 mu m, 67.5% cumulative mass less than 2.5 mu m and 66.2% cumulative mass less than 1.0 mu m Time-course bioavailabil ity results indicated that greater than 95% of the parent compound is clear ed from blood 240 min postexposure. An Sp1 transcription factor consensus s equence 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 expo sure to the timed-pregnant dam. The data obtained on the temporal and spati al regulation of gene expression in the brain indicate that (1) Sp1 DNA-bin ding is developmentally regulated and expressed very highly in actively dev eloping brain regions, and (2) a consequence of the transplacental depositi on of desorbed BaP to the fetus is in utero neurotoxicity.