University of Louisville
Chronic Inflammation Does Not Alter Patterns of Gene Expression in CarcinogenInitiated Lung Cancer
Institution
University of Louisville
Faculty Advisor/ Mentor
Glen McGregor
Abstract
Tobacco smoke is directly related to ~90% of human lung cancers. Relevant physiologic responses to inhaled smoke include the induction of potentially mutagenic adducts in DNA from direct carcinogen exposure and inflammatory responses. We are examining the hypothesis that the carcinogenic potential of environmental mutagens is enhanced by inflammation and that mutagenesis has a direct role in this enhancement. To do this, we are using a mutagen initiated-inflammation promoted mouse model of lung adenocarcinoma followed by tumor analysis using gene expression profiling. We exposed BALB/c mice to a single injection of the cigarette smoke-associated mutagen benzo[a]pyrene (B[a]P) followed by 6 weekly injections of the pulmonary irritant butylated hydroxytoluene (BHT) or vehicle. The mice were examined for tumor burden ~16-32 weeks after B[a]P injection. There were no tumors in control mice or in mice exposed to BHT alone. In contrast, B[a]P alone induced an average of about 1 grossly visible adenoma on the surface of each lung. However, addition of BHT to carcinogen administration drastically increased tumor multiplicity and size. We hypothesized that tumors that arose in the face of chronic inflammation would have different patterns of gene expression. To examine this, we used the Pixcell II laser capture microdissection (LCM) microscope to isolate and capture tumor tissue from three mice that were exposed to B[a]P or from three mice that were exposed to B[a]P /BHT. RNA was extracted and amplified from each sample using Arcturus technology. Affymetrix microarray technology was used to generate and analyze gene expression profiles for >40,000 murine genes. Analysis of the data indicated chronic inflammation did not alter gene expression, that is, patterns of gene expression in tumors that arose in the BHT - and BHT + treatment groups were not significantly different. These data are consistent with the notion that the causative events in inflammation-promoted tumorigenesis occur well before hyperplasia and adenomas are observed. To explore this possibility we are currently examining gene expression profiles in treated but non-dysplastic bronchial epithelium derived from the same mice.
Chronic Inflammation Does Not Alter Patterns of Gene Expression in CarcinogenInitiated Lung Cancer
Tobacco smoke is directly related to ~90% of human lung cancers. Relevant physiologic responses to inhaled smoke include the induction of potentially mutagenic adducts in DNA from direct carcinogen exposure and inflammatory responses. We are examining the hypothesis that the carcinogenic potential of environmental mutagens is enhanced by inflammation and that mutagenesis has a direct role in this enhancement. To do this, we are using a mutagen initiated-inflammation promoted mouse model of lung adenocarcinoma followed by tumor analysis using gene expression profiling. We exposed BALB/c mice to a single injection of the cigarette smoke-associated mutagen benzo[a]pyrene (B[a]P) followed by 6 weekly injections of the pulmonary irritant butylated hydroxytoluene (BHT) or vehicle. The mice were examined for tumor burden ~16-32 weeks after B[a]P injection. There were no tumors in control mice or in mice exposed to BHT alone. In contrast, B[a]P alone induced an average of about 1 grossly visible adenoma on the surface of each lung. However, addition of BHT to carcinogen administration drastically increased tumor multiplicity and size. We hypothesized that tumors that arose in the face of chronic inflammation would have different patterns of gene expression. To examine this, we used the Pixcell II laser capture microdissection (LCM) microscope to isolate and capture tumor tissue from three mice that were exposed to B[a]P or from three mice that were exposed to B[a]P /BHT. RNA was extracted and amplified from each sample using Arcturus technology. Affymetrix microarray technology was used to generate and analyze gene expression profiles for >40,000 murine genes. Analysis of the data indicated chronic inflammation did not alter gene expression, that is, patterns of gene expression in tumors that arose in the BHT - and BHT + treatment groups were not significantly different. These data are consistent with the notion that the causative events in inflammation-promoted tumorigenesis occur well before hyperplasia and adenomas are observed. To explore this possibility we are currently examining gene expression profiles in treated but non-dysplastic bronchial epithelium derived from the same mice.