Protein expression analyses for identifying genotoxic compounds

摘要

The invention relates to a method for screening compounds with (pro-)genotoxic activity by providing a system being capable of expressing a panel of defined proteins, incubating at least a portion of the system with compounds to be screened, and comparing the expression of the proteins in the system with the protein expression in a control system, thereby detecting the (pro-)genotoxic activity. Another object of the invention concerns a method for monitoring the likelihood of developing a physiological and/or pathological condition, which is caused, mediated and/or propagated by the genetic deregulation of proliferation, differentiation and/or damage repair, in response to a compound administered to a mammal in need of such treatment by determining an expression level of defined proteins in a biological sample withdrawn from the mammal. The invention also relates to a kit for screening compounds with (pro-)genotoxic activity comprising antibodies that specifically bind to marker proteins.

主权项

1. A method for screening compounds for genotoxic and/or pro-genotoxic activity comprising the step of determining expression levels of active forms of at least two proteins selected from the group of p-p53 (Ser15), p21, p-H2A.X (Ser139), p-ATM (Ser1981), p-Chk1 (Ser345), p-ATR (Ser428), p-cdc2 (Thr14/Tyr15), Gadd45a and p-Chk2 (Thr68) in a system incubated with one or more compounds in comparison with the expression levels in a system not incubated with the compounds.