Analyzing microarray data with transitive directed acyclic graphs

Test compound one, 5,6-benzoflavone (BNF), was known to act through both the Ah receptor and Nrf2 receptor pathways, while test compounds two and three, 3H-1,2-dithiole-3-thione (D3T) and 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (OLT), were known to act through the Nrf2 receptor pathway. Furthermore, D3T is known to be more potent and efficacious than OLT for Nrf2 activation. OLT has been shown to exhibit 20-50% of the efficacy of D3T for inhibition of alfatoxin-induced heptic foci. Nonetheless, because OLT is an approved drug, it is currently being evaluated in human phase II intervention trials of biomarkers of alfatoxin-related hepatocellular carcinoma. More recently, BNF was shown to be an effective chemopreventive agent in the rat mammary carcinogen model, inhibiting 7,12-dimethylbenz(a)anthracene DNA adduct formation in liver and mammary cells by 96 and 83% respectively. We used microarrays to study the structure activities that lie within the test compounds. Keywords: treatment effect study Twenty female Sprague Dawley rats, were randomly divided into 4 groups of 5 each. Each group of rats were fed with Harlan Teklad Rodent diet, 4% mash diet (Control) or the same formulation containing either, 5,6-benzoflavone (BNF, 1650 mg/kg diet), 3H-1,2-dithiole-3-thione (D3T, 600 mg/kg diet), or 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (OLT, 500 mg/kg diet), for 24 days. The rats were sacrificed with carbon dioxide. The livers were harvested within 3 min, rapidly frozen in liquid nitrogen, and stored at -80oC until they were processed