title: DNA repair during in utero development: a review of the current state of knowledge, research needs, and potential application in risk assessment.
abstract: Exposure to genotoxic chemicals during in utero development may lead to outcomes such as altered gene transcription, mutations, or cell death. Ultimately, such exposures may result in cancer, malformations, or functional deficits. As a mechanism that can limit the impact of genotoxicants in adults, DNA repair may also be an important factor that determines the outcome of the conceptus. This review of the literature examines the current understanding of DNA repair during in utero mammalian development by investigating the importance of maintaining genomic integrity and factors affecting susceptibility, including DNA repair. Most data have been derived from studies in rodent models focusing on DNA repair gene expression, which can vary according to developmental stages, tissues, and DNA repair pathways. Gene expression information is limited for humans but is suggestive that the major repair pathways exist during in utero development. Due to the complexities of DNA repair and its regulation by other pathways, available gene expression data may be limited for clarifying the role of DNA repair as a mechanism controlling the response to in utero exposures to genotoxicants. While not a comprehensive dataset, functional studies assessing in utero DNA repair capacity do demonstrate the variable ability of fetal tissue to remove DNA damage. Data gaps are recognized and recommendations for additional research using stems cells and traditional embryo models are identified. Finally, a brief discussion focuses on how data regarding in utero DNA repair may ultimately be utilized in health risk assessments of genotoxic chemicals.
authors.affiliation: Oak Ridge Institute for Science and Education Postdoctoral Fellow, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA. Electronic address: pachkowski.brian@epa.gov.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Pachkowski
authors.affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.
authors.forename: Kathryn Z
authors.initials: KZ
authors.lastname: Guyton
authors.affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.
authors.forename: Babasaheb
authors.initials: B
authors.lastname: Sonawane
mesh_terms: D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000502:physiology; D005333:Fetus / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D051381:Rats; D018570:Risk Assessment
chemical_list: D009153:Mutagens