Chemotherapy Drugs Mutate DNA in Offspring

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One of the concerns with childhood cancer survivors is whether their future offspring may suffer from DNA damage though mutations induced by the chemotherapy drugs taken when the parent was a child. A recent study raises this concern as results show that chemotherapy drugs do mutate the DNA that is passed on in the offspring of chemotherapy drug treated laboratory mice.

According to a recent study published in the journal Proceedings of the National Academy of Sciences (PNAS), researchers have discovered that common chemotherapy drugs can cause DNA mutations not only in mice that receive treatment, but also in their offspring. What this means is that apparently the germ cell genome in treated mice becomes “destabilized” in such a way from the mutagenic effects of the chemotherapy drugs that the mutations are then passed onto their progeny.

Yuri Dubrova, co-author of the PNAS article was first interested in mutations passed on from parent to progeny when he discovered a little over a decade ago that mice exposed to radiation pass on DNA mutations to their progeny.

“What we found was the biggest surprise of my life,” says Dubrova. “The children [mice offspring] had several times more mutations in their eggs and sperm than their radiation-treated parents…the genomes were unstable, and we still don’t know why.”

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Since then, Dubrova and colleagues have focused on determining whether the chemicals in chemotherapy drugs could cause the same effects—if not more so—because, whereas radiation treatment is localized, chemotherapy is throughout the body.

In the PNAS study, the researchers tested the effects of three common chemotherapy drugs (cyclophosphamide, mitomycin C and procarbazine) on a single small region of the mouse genome. What they found was that DNA mutations within the observed region occurred twice as often in the progeny of treated males than were found in either parent. This suggests that the mutagenic effects of the chemotherapy drugs were responsible for the changes in the progeny DNA and it is likely that numerous other regions were affected as well with mutations.

The authors of the study caution that their results may not apply to humans due to the fact that most people who receive chemotherapy do not have children afterward, and due to a study last year that reported no findings of a significant impact of radiation or chemotherapy on the rate of birth defects in 4,699 children of childhood cancer survivors.

However, mutations can and do accumulate in a genome and may not readily manifest until subsequent generations later. Experts would agree that further studies are needed to confirm what the risks are with chemotherapy drugs resulting in DNA mutations in the offspring of parents who had undergone chemotherapy and/or radiation treatment sometime in their lives before having children.

Image Source: Courtesy of Wikipedia

Reference: "Cancer drugs affect mouse genomes for generations” PNAS (USA) Glen, C. D. & Dubrova, Y. E.

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