Systems toxicology approaches enable mechanistic comparison of spontaneous and cigarette smoke-related XXXX development in the A/J @entity19 model.

@entity8483 @entity19 @entity5 @entity2 @entity9348 @entity105 @entity1981
The A/J @entity19 is highly susceptible to @entity2 induction and has been widely used as a screening model in carcinogenicity testing and chemoprevention studies. However, the A/J @entity19 model has several disadvantages. Most notably, it develops @entity2 spontaneously. Moreover, there is a considerable gap in our understanding of the underlying mechanisms of @entity105 in the A/J @entity19 . Therefore, we examined the differences between spontaneous and cigarette smoke-related @entity2 in the A/J @entity19 model using mRNA and microRNA (miRNA) profiling. Male A/J @entity19 were exposed whole-body to @entity1981 ( @entity1981 ) for 18 months. Gene expression interaction term analysis of @entity2 and surrounding non-tumorous parenchyma samples from animals that were exposed to either 300 mg/m(3) @entity1981 or sham-exposed to fresh air indicated significant differential expression of 296 genes. Ingenuity Pathway Analysis(  ) ( @entity9348 (  )) indicated an overall suppression of the humoral immune response, which was accompanied by a disruption of @entity8483 and glycosaminoglycan metabolism and a deregulation of potentially oncogenic miRNA in @entity5 of @entity1981 -exposed A/J @entity19 . Thus, we propose that @entity1981 exposure leads to severe perturbations in pathways essential for @entity5 recognition by the immune system, thereby potentiating the ability of @entity5 cells to escape from immune surveillance. Further, exposure to @entity1981 appeared to affect expression of miRNA, which have previously been implicated in @entity105 and are thought to contribute to @entity5 progression. Finally, we identified a 50-gene expression signature and show its utility in distinguishing between cigarette smoke-related and spontaneous @entity2 .
