Resistance to DNA damage and enhanced DNA repair capacity in the hypoxia-tolerant blind mole rat, Spalax

The blind mole rat, Spalax, is the only mammalian species, to date, for which spontaneous cancer was never reported and resistance to carcinogens- induced cancers was demonstrated. However, the underlying mechanisms are still poorly understood. The fact that Spalax is also a hypoxia-tolerant and a long-lived species implies for molecular adaptations to prevent genomic instability, which underlies both cancer and aging. We previously demonstrated the up-regulation of transcripts related to DNA replication and repair pathways in Spalax. Yet, to date, no direct experimental evidence for improved genomic maintenance was demonstrated for this species. Here, we show that compared to these of the above-ground rat, Spalax skin fibroblasts in culture resists several types of genotoxic insults, accumulates less genotoxic lesions, and exhibit an enhanced DNA repair capacity. Our results strongly support that this species has evolved efficient mechanisms to maintain DNA integrity as an adaptation to the stressful conditions in the subterranean habitat.