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Effects of THS on cell and molecular mechanisms of healing

Institution: University of California, Riverside
Investigator(s): Manuela Martins-Green, Ph.D.
Award Cycle: 2010 (Cycle 19) Grant #: 19XT-0166 Award: $250,000
Subject Area: General Biomedical Science
Award Type: Exploratory/Developmental Award

Initial Award Abstract
Tobacco smoking is one of the leading avoidable causes of death in the world. With time, it leads to problems with wound healing, cancer, hardening of the arteries, and to liver, lung and kidney disease. Moreover, it also severely affects how people heal. Wounds of smokers and of those exposed to smoking do not close well, potentially remaining as open sores which, with time, can become sites for local infection, spread systemically in the body, and become life-threatening. Furthermore, problematic healing caused by smoke can occur in people of all ages (for example, in children living in the homes of smokers), not only in older individuals as is the case for most smoke-induced ailments. The problem of open sores is not only life-threatening but it also bears heavily on health care costs as people with open wounds frequently need to be hospitalized.

The goal of this application is to determine the effects of Third Hand Smoke on wound healing. During wound healing, a variety of processes triggered by the formation of the clot lead to invasion of the wounded tissue by white blood cells that then mount a defensive reaction against microorganisms and produce molecules that stimulate fibroblasts, the worker cells of the wound. These cells divide to fill the wound, produce extracellular molecules that initially hold the wound together and provide pathways for incoming blood vessels (which oxygenate and nourish wounded tissues), and contract the wound to help in its final closure. It is known that first-hand smoke and secondhand smoke (SHS) inhibit wound healing but nothing is known about the effects of third-hand smoke (THS) on wound healing. THS is composed of the toxins that are released by SHS and accumulate on surfaces such as car seats, dashboards, handles, etc. in cars of smokers. Similarly, it accumulates in upholstery, curtains, carpets in households of smokers.

I propose that chemicals in THS interfere with normal function of the cells in the wound tissue and thereby contribute to the difficulty in healing of wounds and the survival of skin grafts. To address this problem, we will use mice, expose them for 6 months to THS present in their cages and, at the end of the exposure period, we will perform wounds on their backs and study the time course of healing by examining not only the wound areas but also the properties of the tissues. In particular, we will determine if THS increases inflammation that leads to delay of the healing process and, if it inhibits development of microvessels that are critical to bring nutrients and oxygen to the healing tissue.

These studies will lend themselves to preparation of educational materials that can be provided to adults who smoke to raise their awareness of the impact that their smoking can have on their children and elderly parents. Furthermore, these studies will also help adult smokers understand that their family members are severely affected if they undergo surgery and return to a THS-polluted environment because their healing process will be not only be altered but will also be significantly delayed. Finally, the proposed work will benefit the public by providing a better understanding of the cause of impaired healing among individuals who are constantly exposed to Third Hand Smoke, i.e. smokers themselves, children and elderly parents in households of smokers, waiters and waitresses in bars and housekeepers in hotels or houses of smokers.