Methods for identifying the toxic/pathologic effect of environmental stimuli on gene transcription

A method for identifying an effect on transcriptional regulation underlying the occurrence of a pathological reaction to a pharmaceutically active substance, said method comprises the steps of;

• (a) providing a plurality of identical grids, each grid comprising a surface on which is immobilized at predefined regions on said surface a plurality of defined unique oligonucleotide sequences, wherein said sequences comprise a gene or gene fragment obtained from a healthy human;
• (b) exposing human cells, tissue or organ obtained from a human not having said pathological reaction to said pharmaceutically active substance for a sufficient time to affect transcription of mRNA in said cells, tissue or organ;
• (c) extracting, isolating and labeling mRNA from said exposed cells, tissue or organ of step (b);
• (d) exposing human cells, tissue or organ obtained from a human having said pathological reaction to said pharmaceutically active substance for a sufficient time to affect transcription of mRNA in said cells, tissue or organ;
• (e) extracting, isolating and labeling mRNA from said cells, tissue or organ of step (d);
• (f) hybridizing the mRNA of step (c) to a first identical grid to produce a first hybridization pattern;
• (g) hybridizing the mRNA of step (e) to a second identical grid to produce a second hybridization pattern;
• (h) comparing the first pattern of step (f) and the second pattern of step (g) to identify any difference between said first pattern and second pattern, said difference being indicative of an effect on transcriptional regulation of said cells, tissue or organ in said human having said pathological reaction.