3H-1,2-dithiole-3-thione (D3T), an inducer of antioxidant and phase 2 genes, is 
known to enhance the detoxification of environmental carcinogens, prevent 
neoplasia, and elicit other protective effects. However, a comprehensive view of 
the regulatory pathways induced by this compound has not yet been elaborated. 
Fischer F344 rats were gavaged daily for 5 days with vehicle or D3T (0.3 
mmol/kg). The global changes of gene expression in liver were measured with 
Affymetrix RG-U34A chips. With the use of functional class scoring, a 
semi-supervised method exploring both the expression pattern and the functional 
annotation of the genes, the Gene Ontology classes were ranked according to the 
significance of the impact of D3T treatment. Two unexpected functional classes 
were identified for the D3T treatment, cytosolic ribosome constituents with 90% 
of those genes increased, and cholesterol biosynthesis with 91% of the genes 
repressed. In another novel approach, the differentially expressed genes were 
evaluated by the Ingenuity computational pathway analysis tool to identify 
specific regulatory networks and canonical pathways responsive to D3T treatment. 
In addition to the known glutathione metabolism pathway (P = 0.0011), several 
other significant pathways were also revealed, including antigen presentation (P 
= 0.000476), androgen/estrogen biosynthesis (P = 0.000551), fatty acid (P = 
0.000216), and tryptophan metabolism (P = 0.000331) pathways. These findings 
showed a profound impact of D3T on lipid metabolism and 
anti-inflammatory/immune-suppressive response, indicating a broader 
cytoprotective effect of this compound than previously expected.