Molecular analysis of 4NQO-induced rat tongue cancers using cDNA microarrays - for a purpose of clinical application

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Here we report that use of cDNA microarrays to measure global patterns of gene expression in 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinoma tissue. Measurements of gene expression have been the basis for molecular differentiation of two strains of the rats, highly susceptible Dark-Agouti (DA) rat and poorly susceptible Wistar/Furth (WF) rat (Kitano et al, Jpn J Cancer Res 83, 845-50, 1992 ; Kitano et al, Jpn J Cancer Res 87, 1097-101, 1996). For quantification of the gene expression, fluorescence derived from microarrays hybridized in parallel to control (Cy3-labelled) and 4-nitroquinoline 1-oxide-induced rat tongue cancer (Cy5-labelled) cDNA samples of the two strains of rats were overlayed and analyzed. The expression factor --- evaluated from quadruplicate hybridization --- was determined as a mean value according to the ratios of the Cy5/Cy3 signal intensities. More than 3-fold increases or decreases of the gene expression ratios were regarded as relevant in this experiment. The genes which were up-regulated and down-regulated in a 4NQO-induced tongue cancer (15mm in the diameter) of a DA rat was 337 and 220, respectively, and another 4NQO-induced tongue cancer (5mm in the diameter) developed in a WF rat was 182 and 81, respectively. Regarding the genes previously described as the candidates for QTLs involved in susceptibility of tongue carcinogenesis in the rat (Tanuma et al, Cancer Res 58, 1660-4, 1998 ; Tanuma et al, Jpn J Cancer Res 92, 610-6, 2001 ; Tanuma et al, Int J Cancer 102, 638-42, 2002), microarray analysis demonstrated that the tongue cancers showed a distinct difference in gene expression ratios, for example of NQO1 gene, between the DA rat and WF rat.These results indicate that the DA rat and WF rat possibly show a distinct signature of differential gene expression in their tongue cancers of which histologic types are the same, I.e., squamous cell carcinoma.