Genomic and transcriptional alterations in mouse fetus liver after transplacental exposure to cigarette smoke.
The transplacental exposure of fetuses to maternal cigarette smoke may increase the risk of developmental impairments, congenital diseases, and childhood cancer. The whole-body exposure of Swiss mice to environmental cigarette smoke (ECS) during pregnancy decreased the number of fetuses per dam, placenta weight, and fetus weight. ECS increased DNA adducts, oxidative nucleotide alterations, and cytogenetic damage in fetus liver. Evaluation by cDNA array of 746 genes showed that 61 of them were expressed in fetus liver under basal conditions. The oral administration of N-acetylcysteine (NAC) during pregnancy enhanced the expression of three genes only, including two glutathione S-transferases and alpha1-antitrypsin precursor, whose deficiency plays a pathogenetic role in congenital emphysema. Transplacental ECS upregulated the expression of 116 genes involved in metabolism, response to oxidative stress, DNA and protein repair, and signal transduction. NAC inhibited the ECS-related genetic damage and upregulation of most genes. ECS stimulated pro-apoptotic genes and genes downregulating the cell cycle, which may justify growth impairments in the developing fetus. Thus, both genetic and epigenetic mechanisms were modulated by ECS. Moreover, hypoxia-related genes and several oncogenes and receptors involved in proliferation and differentiation of leukocytes were induced in the fetal liver, which also bears hematopoietic functions.
Izzotti
Alberto
A
Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132, Italy.
Balansky
Roumen M
RM
Cartiglia
Cristina
C
Camoirano
Anna
A
Longobardi
Mariagrazia
M
De Flora
Silvio
S
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia; D018736:DNA Adducts / Q000378:metabolism; D004260:DNA Repair; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016678:Genome; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D018811:Maternal Exposure; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010298:Parity / Q000187:drug effects; D010920:Placenta / Q000033:anatomy & histology / Q000187:drug effects; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects; D014158:Transcription, Genetic
D016588:Anticarcinogenic Agents; D018736:DNA Adducts; D000111:Acetylcysteine