Study in Genes and Development showed that 48 genes can together forecast susceptibility to toxic compound MNNG at a 94% accuracy.

MIT researchers report that variation in gene expression underlies the fact that people react differently to toxic agents. Studying N-methyl-N’-nitro-N-nitrosoguanidine (MNNG), they found that a set of 48 genes can predict how harmful the compound will be to a given individual at 94% accuracy.

The investigators used a high-throughput growth inhibition assay across a panel of 24 cell lines derived from unrelated, healthy individuals with diverse ancestry. The cell lines 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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