Abstract
Bats are unusual mammals, with the ability to fly, and long lifespans. In addition, bats have a low incidence of cancer, but the mechanisms underlying this phenomenon remain elusive. Here we discovered that bat cells are more resistant than human and mouse cells to DNA damage induced by genotoxic drugs. We found that bat cells accumulate less chemical than human and mouse cells, and efficient drug efflux mediated by the ABC transporter ABCB1 underlies this improved response to genotoxic reagents. Inhibition of ABCB1 triggers an accumulation of doxorubicin, DNA damage, and cell death. ABCB1 is expressed at higher levels in several cell lines and tissues derived from bats compared to humans. Furthermore, increased drug efflux and high expression of ABCB1 are conserved across multiple bat species. Our findings suggest that enhanced efflux protects bat cells from DNA damage induced by genotoxic compounds, which may contribute to their low cancer incidence.
Highlights
Bats are unusual mammals, with the ability to fly, and long lifespans
To explore DNA damage resistant mechanisms in bat, we first examined the DNA damage response in bat, human and mouse cells exposed to different DNA damaging treatments
To determine if one of these transporters is required for doxorubicin efflux in P. alecto cells, we reduced the expression of each gene in PaKiT03 cells via small-interfering RNA-mediated knockdown (Fig. 5b) and examined the effects on intracellular doxorubicin accumulation by flow cytometry (Fig. 5c)
Summary
With the ability to fly, and long lifespans. In addition, bats have a low incidence of cancer, but the mechanisms underlying this phenomenon remain elusive. We discovered that bat cells are more resistant than human and mouse cells to DNA damage induced by genotoxic drugs. Our findings suggest that enhanced efflux protects bat cells from DNA damage induced by genotoxic compounds, which may contribute to their low cancer incidence. Most cancer research utilises cancer-prone, short-lived animals such as mouse and rat, which are amenable to genetic manipulation These model organisms share some tumour suppressor mechanisms with humans, emerging evidence suggests that long-lived mammals have evolved unique and robust anti-cancer strategies[2]. Long-lived mammals with an extremely low incidence of cancer[2,10] They are the second largest order of mammals in the world[11], the only mammal capable of poweredwing flight, and an asymptomatic reservoir for many deadly viruses[10]. Austad and Fischer[13] defined the longevity quotient (LQ) which takes the consideration of body mass in the estimated maximum lifespan of individual mammalian species
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