Abstract
Naked mole rat is the long-lived and tumor-resistant rodent. Naked mole rat possesses multiple adaptations that may contribute to longevity and cancer-resistance. Higher activity of DNA excision repair systems and their faster recovery after genotoxic impact as compare with Mus musculus directly demonstrated in our previous investigation contribute to longevity and cancer resistance of naked mole rat. In the present study the DNA-damage-induced apoptosis in naked mole rat fibroblasts was studied using conventional methods. The ability of naked mole rat cells to undergo regulated cell death in response to genotoxic stress is another group of cell defense mechanisms. Naked mole rat skin fibroblasts were demonstrated to be much more resistant towards proapoptotic reagents methyl methanesulfonate, 5-fluorouracil and etoposide as compared with fibroblasts of Mus musculus. Naked mole rat cells have demonstrated limited apoptotic response and seem to undergo also other-type regulated cell death under severe genotoxic stress.
Highlights
Naked mole rat (NMR, Heterochephalus glaber) is the extremely long-lived and tumorresistant small rodent
Summarizing, our results suggest that NMR has more efficient nucleotide excision repair (NER) and base excision repair (BER) systems than the mouse, which may contribute to longevity and cancer resistance of this species
The skin fibroblasts from NMR vs. MMU, e.g. NSF8 and 3T3 cells, respectively, were treated in the time- and dose- dependent manner with methyl methane sulfonate (MMS), 5-fluorouracil and etoposide
Summary
Naked mole rat (NMR, Heterochephalus glaber) is the extremely long-lived and tumorresistant small rodent. We have demonstrated that NMR cells display more efficient excision repair than mouse cells [6]. Time course of transcript levels of the key BER and NER proteins for most of mRNAs no sharp fluctuations was detected for both cells types, especially for NMR. NMR cell extracts were more efficient at removing uracil and at cleaving the AP-site than the mouse ones. A comparative evaluation of the specific excision efficiency makes it possible to compare NER system activity in cell extracts samples. Measurement of specific excision reaction demonstrated that all NMR extracts were more efficient than mouse ones at bulky lesion elimination. Summarizing, our results suggest that NMR has more efficient NER and BER systems than the mouse, which may contribute to longevity and cancer resistance of this species
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