Study in Genes and Development shows that 48 genes can predict susceptibility to toxic compound MNNG.



MIT researchers have found that cells from different people don’t all react the same way when exposed to N-methyl-N’-nitro-Nnitrosoguanidine (MNNG). They found that a set of 48 genes can predict how harmful the compound will be to a given individual at 94% accuracy.


Toxic agents such as MNNG create lesions in DNA, provoking the cell to defend itself with a variety of DNA-repair and other pathways. However, every individual expresses slight differences in the genes involved in those pathways.


The investigators used a high-throughput growth inhibition assay across the panel of cell lines, which included control cell lines with very high or very low MNNG sensitivity. The team also monitored MNNG-induced apoptosis in the cell lines and found a positive correlation with MNNG sensitivity.


Several of the 48 genes have already been linked to cancer, but the team cautions that it was not known that their expression is already altered before exposure to the DNA damaging agent.


This study is specific to MNNG, but similar efforts are under way to predict individuals’ responses to other toxic agents including cisplatin and temozolomide.


Results from the MNNG investigation appear in the September 19 online edition of Genes and Development.








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