Radioresistance of bone marrow stromal and hematopoietic progenitor cell lines derived from Nrf2-/- homozygous deletion recombinant-negative mice.

AIM

We determined whether bone marrow from Nrf2(-/-) compared with Nrf2(+/+) mice differed in response to the oxidative stress of continuous marrow culture, and in radiosensitivity of derived stromal and interleukin-3 (IL-3)-dependent hematopoietic progenitor cells.

MATERIALS AND METHODS

Hematopoiesis longevity in Nrf2(-/-) was compared with Nrf2(+/+) mice in long-term bone marrow cultures. Clonogenic irradiation survival curves were performed on derived cell lines. Total antioxidant capacity at baseline in nonirradiated cells and at 24 hours after 5 Gy and 10 Gy irradiation was quantitated using an antioxidant reductive capacity assay.

RESULTS

Long-term cultures of bone marrow from Nrf2(-/-) compared to Nrf2(+/+) mice demonstrated equivalent longevity of production of total cells and hematopoietic progenitor cells forming multi-lineage hematopoietic colonies over 26 weeks in culture. Both bone marrow stromal cell lines and Il-3-dependent hematopoietic progenitor cell lines derived from Nrf2(-/-) mouse marrow cultures were radioresistant compared to Nrf2(+/+)-derived cell lines. Both DNA repair assay and total antioxidant capacity assay showed no defect in Nrf2(-/-) compared to Nrf2(+/+) stromal cells and IL-3-dependent cells.

CONCLUSION

The absence of a functional Nrf2 gene product does not alter cellular interactions in continuous marrow culture, nor response to dsDNA damage repair and antioxidant response. However, lack of the Nrf2 gene does confer radioresistance on marrow stromal and hematopoietic cells.