A lethal epigenetic cocktail

November 26, 2012

There are two deeply disturbing properties of epigenetic inheritance that have been receiving much attention of late. The first is the ability of certain classes of chemicals to cause epigenetic changes that can be transmitted transgenerationally. The second is the propensity of genetically stable tumor cells to display great epigenetic variation, driving their evolution and malignancy.

 Manikkam et al [PLOS ONE 7(9):e46249] report that Dioxin, a potent epimutagen, can induce multiple adult onset disease in the F3 generation when administered to gestating female rats. In another important study Ujvari and coworkers (Proc Biol Sci. 2012 Nov 7. [Epub ahead of print]) find that a bizarre transmissable facial cancer in the Tasmanian Devil, although genomically stable, undergoes extensive epigenetic changes that drive its tumorigenicity. Because of this variability the tumors evolves over time, and these changes can be transmitted to other animals through bodily contact. This rare marsupial has been pushed to the edge of extinction by this cancer.

Connecting these two sets of observations, it seems highly possible that exposure of human populations to epimutagenic agents could induce rapidly evolving and extremely lethal cancers. Moreover, it is also possible that subsequent generations could inherit this genetic alteration.

Epigenetic investigations have focused largely on use of therapies that target methylation site next to controller elements of various oncogenes, as described in a recent Kalorama report. There is a high probability that combining epigenetic drugs with conventional therapies could stop tumor growth and at the same time slow down the uncontrolled variability of cancer that enables it to outrun therapeutic intervention.

At the same time, there is a pressing need for studies that investigate the role of environmental epimutagens in driving disease in both animal and  human populations.

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