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Tobacco Alteration of TGF Beta3 Control of Palatogenesis

Institution: University of Southern California
Investigator(s): Charles Shuler, D.M.D, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11RT-0064 Award: $680,175
Subject Area: General Biomedical Science
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Birth defects that affect the head and face are a common type of malformation. They occur at a rate of approximately one per 600 births. The risks for these types of birth defects are increased by both the inheritance and fetal exposure to drugs and chemicals that alter the developmental process. The incidence of birth defects is also increased in specific ethnic groups with Asians and Hispanics affected at rates approaching one per 400 births. An individual or ethnic group that has an increased risk for birth defects of the face increases the risk by using drugs or chemicals that alter facial development. It has been shown that mothers who smoke tobacco greatly increase the chances that their babies will be born with a cleft lip and/or cleft palate. The tobacco smoke contains chemicals that enter the mother’s system and interact with the baby changing the way the face develops. Some people have an even greater risk for the birth defect potential of tobacco because they have inherited a specific set of genes from their parents.

Genes that belong to the (TGFb) transforming growth factor beta family have been associated with increasing the birth defect potential of tobacco. Transforming growth factor betas are small proteins that attach to the surface of cells and instruct the cells to perform specific functions. In animals, it has been shown that disrupting the function of these small proteins can induce a cleft palate. In this project, we will study the interaction of tobacco products and the transforming growth factor beta signaling mechanism. Understanding how they interact will provide new insight into the mechanisms that cause the formation for cleft lip/palate birth defects. In the future the results of these studies may help provide information that can be used in prenatal education for mothers to reduce the risk that their child could be born with a facial birth defect. The results could also help develop strategies to identify people with an increased risk for birth defects due to interactions of their inherited genes and exposure to environmental chemicals, such as tobacco.
Publications

Effect of N -nitrosonornicotine (NNN) on murine palatal fusion in vitro.
Periodical: Toxicology Index Medicus:
Authors: Saito T, Cui X-M, Yamamoto T, Shiomi N, Bringas P, Shuler CF ART
Yr: 2005 Vol: 207 Nbr: Abs: Pg: 475 - 485

Effect of N-nitrosonornicotine (NNN) on murine palatal fusion in vitro
Periodical: Toxicology Index Medicus:
Authors: Saito, T, Cui, X-M, Yamamoto, T, Shiomi, N, Bringas, P & Shuler, CF ART
Yr: 2005 Vol: 207 Nbr: Abs: Pg: 475-485

Mitogen-activated protein Kinase mediates N-nitrosonornicotine (NNN) inhibition of palatal shelf fusion through nicotinic acetylcholine receptor
Periodical: Toxicology Index Medicus:
Authors: saito,T Cui, X-M, Yamamoto, T, Shiomi, N, Bringas, P & Shuler, CF ART
Yr: 0 Vol: Nbr: Abs: Pg: