These included xenobiotic metabolism, oxidative stress and p53 signalling ( Supplementary Table 2). In support of these results we also noticed a highly similar dose–response increase in BPDE–DNA adducts in both the lungs and the liver ( Table 2). These findings suggest Estrogen antagonist that BaP administration by oral gavage resulted in the distribution of BaP

in its unmetabolized form to the lungs (i.e., escaping detoxification in the liver), where it was metabolized to BPDE by CYP enzymes leading to DNA adduct formation. BaP is a well known lung carcinogen. Development of lung tumours after BaP administration either by intra peritoneal injection or by oral gavage has been reported by Gunning et al. (2003) and Katiyar et al. (1993). One of the mechanisms by which BaP is hypothesized to promote lung carcinogenesis is through induction of oxidative stress. In keeping with this model, we observed changes in the pulmonary expression of many genes that are associated with oxidative stress in BaP-treated Selleck GDC-0980 samples. These genes include NAD(P)H

dehydrogenase, quinone 1, sulfiredoxin 1 homolog, genes belonging to glutathione S-transferase family, glutamate-cysteine ligase, carbonyl reductase 3, thioredoxin reductase 1, heme oxygenase (decycling) 1 ( Supplementary Table 1). We also observed altered expression of several genes that are implicated in tumour promotion in the lungs including heat shock protein 1A, Rapamycin prostaglandin-endoperoxide synthase 2, chemokine (C-X-C motif) ligand 12, and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein F ( Supplementary Table 1). Our results, along with existing literature on the carcinogenic potential of BaP, support the notion that oral administration of high doses of BaP can have a carcinogenic impact on various tissues, including the lungs. In addition to the expected perturbations in the pathways that are known to be altered in response to BaP and were observed in both liver and lung, we also noted dramatic downregulation

of genes involved in the B-cell receptor signalling pathway (Table 3) that were unique to the lung. B cells are a critical component of the adaptive immune response, which provides protection from a diverse range of potential pathogens (Martensson et al., 2010). A detailed inspection of the transcriptional response to BaP in our study revealed that every component of the B cell activation pathway was suppressed transcriptionally. In addition, expression levels of several critical B-cell transcription factors implicated in regulating the expression of specific Ig isotypes and B cell specific genes such as NFATc, Spi-B, Ikaros, and FoxP1 were also significantly reduced ( Supplementary Table 1).