A Novel Mouse Model of Thirdhand Smoke-Induced Childhood Leukemia
Abstracts
Initial Award Abstract |
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Lymphoblastic leukemia (ALL) is the most common cancer of childhood. Of note, the risk of ALL has been increasing. The development of childhood ALL involves genetic and epigenetic processes, but how these factors are influenced by pre-natal and early life exposures is poorly understood. Thirdhand smoke (THS) has gained wide attention in recent years as a newly described health risk. THS includes tobacco smoke residues in indoor environments that remain, react and/or re-emit from materials and/or re-suspend from surfaces. Vulnerable populations are believed to be infants living in current or previously smoked in households. Since infants typically spend more time indoors and have age-specific behaviors, i.e., crawling and ingesting non-food items, they are often in close contact with surfaces and dust. As a result even low doses of THS constituents may represent a long-term health hazard to children. The hypothesis underlying the current proposal is that THS exposure interacts with underlying genetics to place children at risk for the development of ALL. The broad long-term goals of our work are to understand how exposure to THS impacts the development of childhood leukemia and to use this knowledge to decrease rates of pediatric leukemia. In order to pursue these long-term goals, we herein propose a pilot study to determine which of two animal models of childhood leukemia will be most appropriate for future studies of developmental exposure windows and of the epigenetic and genetic mechanisms that underlie the ability of tobacco to contribute to childhood leukemia. One model utilizes animals that have a high frequency of development of ALL. This model enables assessment of how THS exposure may accelerate disease in individuals who are highly susceptible to ALL. The second model utilizes animals that have genetic changes the predispose to ALL, but only develop disease at low frequency. This model enables assessment of how THS exposure may initiate the development of ALL. This pilot study will enable the identification of a model to be used for in depth investigation of when and how tobacco exposure can cause childhood leukemia. This work is important for formulating appropriate preventive strategies including educating health practitioners, families, public health providers and organizations regarding the risks of tobacco exposure. |
