Undesirable Consequences

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Science  27 Aug 2010:
Vol. 329, Issue 5995, pp. 997
DOI: 10.1126/science.329.5995.997-b

One reason cancer cells are so tenacious is that they have often lost the normal apoptotic regulators that would trigger cell death. Thus, treatments that reduce apoptosis would be expected to promote tumorigenesis. Surprisingly, Labi et al. and Michalak et al. found that mice made deficient in the proapoptotic protein Puma showed a lower incidence of lymphoma after exposure to ionizing radiation. Independently, the authors concluded that the explanation has to do with the effects of radiation on hematopoietic stem cells and their contribution to cancer. When normal animals were exposed to radiation, cells in the bone marrow or thymus died, which stimulated their replenishment through proliferation of hematopoietic stem cells. Multiple rounds of radiation made these animals more likely to develop DNA damage associated with excessive cell division, and this led to tumor formation. On the other hand, mice missing Puma exhibited diminished cell death in response to radiation, and hence suffered less replication stress on their hematopoietic stem cells. These results may have implications for cancer patients who undergo similar rounds of γ-irradiation or for therapeutic strategies using agents that act like Puma to stimulate cell death: Either treatment might have the potential to promote formation of a secondary cancer.

Genes Dev. 24, 1602; 1608 (2010)

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