Bowhead whales, the world鈥檚 longest-lived mammals, are seldom affected by cancer and this may partly be down to their cells repairing damaged DNA very efficiently.
Large animals have more cells than smaller ones, so they should be more likely to get cancer, but this doesn鈥檛 seem to be the case. This unexpected phenomenon is known as Peto鈥檚 paradox.
In fact, many massive animals have very low rates of cancer, including bowhead whales (Balaena mysticetus), which can weigh more than 80,000 kilograms and live for over 200 years. Last year, a study found that one possible reason for this is that bowhead whales have more copies of genes that suppress the development of cancer.
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Now, at the University of Rochester in New York and her colleagues have studied how well skin cells from different animals repair a type of genetic damage in which both strands of the DNA molecule are broken. Such 鈥渄ouble-strand breaks鈥� are known to increase the risk of cancer.
To do this, the researchers used an enzyme to create double-strand breaks in the cells of humans, cows, mice and bowhead whales. They also inserted a gene into the cells that produced a fluorescent green protein following repair of the damaged DNA.
By imaging the cells, the team found that more than twice as many of the damaged bowhead whale cells repaired the breaks in DNA compared with human, cow and mouse cells.
What鈥檚 more, the human, cow and mouse cells most often deleted several DNA letters during the repair process, but for the most part bowhead whale cells accurately repaired the DNA or introduced just a single DNA letter during repair. Adding or deleting letters changes the DNA sequence, which means a gene may not function properly and this can lead to cancer
The researchers also found that a protein called CIRBP, which is involved in repairing DNA, was at higher levels in the bowhead whale cells compared with human, cow and mouse cells.
To test whether this might increase the efficiency of DNA repair, the team genetically modified human and mouse cells to produce high levels of the version of CIRBP found in bowhead whales. These tweaked human and mouse cells were able to repair double-strand breaks about twice as efficiently compared with ordinary cells.
鈥淭his is an excellently done study that unveils an important contributing mechanism as to why bowhead whales resist cancer and live so long,鈥� says at the University of Bologna in Italy.
鈥淚f we can regulate, somehow, our own CIRBP protein, that could absolutely be a strategy to reduce DNA damage in humans,鈥� he says. 鈥淭he work highlights how comparing different animals can be very important in pushing forward our understanding of longevity 鈥� we need to exploit the experiments that evolution already did for us.鈥�
However, experiments in cells aren鈥檛 sufficient to understand the mechanisms of cancer, says at Arizona State University. 鈥淏ecause it attacks the very essence of multicellular organisation, the discoveries obtained from genetic or cellular studies must be validated at the organismal level.鈥�
bioRxiv
