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

Abstract

Blind mole rats of the genus Spalax are the only mammalian species to date for which spontaneous cancer has never been reported and resistance to carcinogen-induced cancers has been demonstrated. However, the underlying mechanisms are still poorly understood. The fact that Spalax spp. are also hypoxia-tolerant and long-lived species implies the presence of molecular adaptations to prevent genomic instability, which underlies both cancer and aging. We previously demonstrated the upregulation of transcripts related to DNA replication and repair pathways in Spalax. Yet, to date, no direct experimental evidence for improved genomic maintenance has been demonstrated for this genus. Here, we show that compared with skin fibroblasts of the above-ground rat, Spalax carmeli skin fibroblasts in culture resist several types of genotoxic insult, accumulate fewer 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.