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Double the Mutations

Irradiated sperm of young male mice induce mutations in eggs upon fertilization, a phenomenon that may pose risks for the children of cancer survivors.

By | January 30, 2012

image: Double the Mutations WIkimedia Commons

WIKIMEDIA COMMONS

Many mouse studies have shown that radiation treatment can cause germline mutations, which can then be passed onto subsequent generations. Now, new research in mice takes this idea one step further: this mutagenic environment can be transferred from sperm to eggs upon fertilization, doubling the mutations in the resulting embryos.

The study, published today (January 30) in the Proceedings of the National Academy of Sciences, raises health concerns for children of young cancer survivors, most of whom have been through multiple rounds of radiation treatment. “This result is now so solid that I think we can’t ignore it,” said radiologist Keith Baverstock from the University of Eastern Finland, who was not involved in the research. “It is an important result because these drugs and radiation are all we really have to treat cancer.”

Baby mice sired by fathers exposed to any of a variety of radiation types—chemical, ionizing, and chemotherapeutic—all have a far higher mutation rate than expected by chance. “The children of irradiated mice are unstable,” said Yuri Dubrova, a geneticist at the University of Leicester “They show quite high rate by which mutations occur in the germ cells, egg and sperm, and same is true for their somatic cells.”

To further study the effects of chemotherapeutic radiation, Dubrova and his colleagues gave three commonly-used chemotherapy drugs to male mice, with doses reflecting those of people adjusted to body size. He then bred them with females of a different strain to easily differentiate between their alleles in the offspring.

Dubrova found that DNA in the male pups’ sperm and bone marrow, the latter representing somatic cells broadly, had significantly more mutations than controls in a “junk” region of DNA used for the analysis. But when he analyzed the alleles more closely, he found that the mutations were not just in chromosomes from the irradiated fathers: the maternal alleles also carried the same elevated mutation rate. Somehow the mutagenesis in male mice, which occurred weeks before mating, affected DNA from females as well.

It’s a result Dubrova’s group has gotten before, but “the point that also the maternal allele is destabilized has been brought up here at a larger scale,” geneticist Peter de Boer of the Radboud University Nijmegen Medical Centre, who was not involved in the research, wrote in an email to The Scientist.

Dubrova worries that the risk of mutations in not only the sperm of irradiated male mice, but also the eggs of their mates, may have implications for the children conceived by cancer survivors months or even years after radiation treatments. While a large study on the cancer risk in children of young cancer patients in Finland found no increase in cancer risk in the children of radiation patients, Dubrova thinks it’s worth looking into further. “Our data indicate that one should start analyzing whether the same is true for humans,” he said.

However, Dubrova isn’t exactly sure how this happens. “The only thing that is absolutely clear here is that the mechanism is not genetic; it’s epigenetic,” he said. “We are working now like mad trying to figure out what went wrong with the offspring using all kinds of omics available to us.”

 

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Avatar of: Brian Hanley

Brian Hanley

Posts: 66

January 31, 2012

While this may be "higher than chance" that's still not much, and there are reasons to be cautious about suggesting it is a major concern. All humans are mutants. Even our cells are, strictly speaking, a quasi-individual, not entirely identical with each other.

In addition to the cited large-scale study showing no evidence of increase in cancer risk, but there is the example of the "Atomic Soldiers" who were stationed in foxholes 1/4 mile from one of the Alamogordo tower tests. They marched to ground zero with no protective gear, disassembled their rifles, reassembled them, marched out. Every one got severe radiation sickness. Every one survived. Every one married had children, all normal. All survived at least 20 years and all were dead of cancer in 25 years.

Also, humans are not mice. If one examines the radiation dose-response curve for humans, we are outliers. We have roughly the radiation dose-response of a 1,000 pound cow, i.e. 10 times what wold be expected based on body-mass alone. All the other mammals fall in line pretty well. Even if this observation turns out to be real and not a lab artifact, it won't necessarily mean that it happens in humans.

There is also the unknown mechanism that affects evolutionary expression in which stress de-represses genes. This is probably how it happens that evolution can apparently operate in phenotypic leaps without violating the laws of probability and physics we know. Perhaps there is some relationship.

This is interesting to study and I think it should be.

But it doesn't have significant implication for patients, who already have plenty to worry about.

Avatar of: agelbert

agelbert

Posts: 50

January 31, 2012

Brian Hanley says all humans are mutants. What a ridiculously laughable statement about the very real difference between pathological mutations (over 98 percent!) and species favoring mutations (few and far between).

What next, Brian? Will you tell us that Fukushima was good for us? Will you expound on the incredibly unscientific meme among the pro-nuclear power plant crowd that ionizing radiation INSIDE the human body from breathing or eating food contaminated with radioisotopes is equivalent to a few x-rays or flying above 30,000 feet? Never mind that these isotopes are inside people 24/7 and x-rays or flying are relatively brief. Never mind the gamed exposure criteria that YOU support that only measures dosage from OUTSIDE the body so you can pretend ALPHA radiation can't destroy DNA because it "can't go through a sheet of paper". You talk about the "atomic soldiers" but conveniently leave out Navajo uranium miners and certain communities in Utah during the atomic testing program. And last but not least the Bikini island population deformed babies, high infant mortality and thyroid cancer don't seem to register as related to genetic radiation damage to you.

You people just don't WANT to get it. Denying reality while pretending to be scientific should be subject to criminal penalties.

Read the code killers and get educated. You are a danger to your family.
http://acehoffman.org/

Avatar of:

Posts: 0

January 31, 2012

While this may be "higher than chance" that's still not much, and there are reasons to be cautious about suggesting it is a major concern. All humans are mutants. Even our cells are, strictly speaking, a quasi-individual, not entirely identical with each other.

In addition to the cited large-scale study showing no evidence of increase in cancer risk, but there is the example of the "Atomic Soldiers" who were stationed in foxholes 1/4 mile from one of the Alamogordo tower tests. They marched to ground zero with no protective gear, disassembled their rifles, reassembled them, marched out. Every one got severe radiation sickness. Every one survived. Every one married had children, all normal. All survived at least 20 years and all were dead of cancer in 25 years.

Also, humans are not mice. If one examines the radiation dose-response curve for humans, we are outliers. We have roughly the radiation dose-response of a 1,000 pound cow, i.e. 10 times what wold be expected based on body-mass alone. All the other mammals fall in line pretty well. Even if this observation turns out to be real and not a lab artifact, it won't necessarily mean that it happens in humans.

There is also the unknown mechanism that affects evolutionary expression in which stress de-represses genes. This is probably how it happens that evolution can apparently operate in phenotypic leaps without violating the laws of probability and physics we know. Perhaps there is some relationship.

This is interesting to study and I think it should be.

But it doesn't have significant implication for patients, who already have plenty to worry about.

Avatar of:

Posts: 0

January 31, 2012

Brian Hanley says all humans are mutants. What a ridiculously laughable statement about the very real difference between pathological mutations (over 98 percent!) and species favoring mutations (few and far between).

What next, Brian? Will you tell us that Fukushima was good for us? Will you expound on the incredibly unscientific meme among the pro-nuclear power plant crowd that ionizing radiation INSIDE the human body from breathing or eating food contaminated with radioisotopes is equivalent to a few x-rays or flying above 30,000 feet? Never mind that these isotopes are inside people 24/7 and x-rays or flying are relatively brief. Never mind the gamed exposure criteria that YOU support that only measures dosage from OUTSIDE the body so you can pretend ALPHA radiation can't destroy DNA because it "can't go through a sheet of paper". You talk about the "atomic soldiers" but conveniently leave out Navajo uranium miners and certain communities in Utah during the atomic testing program. And last but not least the Bikini island population deformed babies, high infant mortality and thyroid cancer don't seem to register as related to genetic radiation damage to you.

You people just don't WANT to get it. Denying reality while pretending to be scientific should be subject to criminal penalties.

Read the code killers and get educated. You are a danger to your family.
http://acehoffman.org/

Avatar of:

Posts: 0

January 31, 2012

While this may be "higher than chance" that's still not much, and there are reasons to be cautious about suggesting it is a major concern. All humans are mutants. Even our cells are, strictly speaking, a quasi-individual, not entirely identical with each other.

In addition to the cited large-scale study showing no evidence of increase in cancer risk, but there is the example of the "Atomic Soldiers" who were stationed in foxholes 1/4 mile from one of the Alamogordo tower tests. They marched to ground zero with no protective gear, disassembled their rifles, reassembled them, marched out. Every one got severe radiation sickness. Every one survived. Every one married had children, all normal. All survived at least 20 years and all were dead of cancer in 25 years.

Also, humans are not mice. If one examines the radiation dose-response curve for humans, we are outliers. We have roughly the radiation dose-response of a 1,000 pound cow, i.e. 10 times what wold be expected based on body-mass alone. All the other mammals fall in line pretty well. Even if this observation turns out to be real and not a lab artifact, it won't necessarily mean that it happens in humans.

There is also the unknown mechanism that affects evolutionary expression in which stress de-represses genes. This is probably how it happens that evolution can apparently operate in phenotypic leaps without violating the laws of probability and physics we know. Perhaps there is some relationship.

This is interesting to study and I think it should be.

But it doesn't have significant implication for patients, who already have plenty to worry about.

Avatar of:

Posts: 0

January 31, 2012

Brian Hanley says all humans are mutants. What a ridiculously laughable statement about the very real difference between pathological mutations (over 98 percent!) and species favoring mutations (few and far between).

What next, Brian? Will you tell us that Fukushima was good for us? Will you expound on the incredibly unscientific meme among the pro-nuclear power plant crowd that ionizing radiation INSIDE the human body from breathing or eating food contaminated with radioisotopes is equivalent to a few x-rays or flying above 30,000 feet? Never mind that these isotopes are inside people 24/7 and x-rays or flying are relatively brief. Never mind the gamed exposure criteria that YOU support that only measures dosage from OUTSIDE the body so you can pretend ALPHA radiation can't destroy DNA because it "can't go through a sheet of paper". You talk about the "atomic soldiers" but conveniently leave out Navajo uranium miners and certain communities in Utah during the atomic testing program. And last but not least the Bikini island population deformed babies, high infant mortality and thyroid cancer don't seem to register as related to genetic radiation damage to you.

You people just don't WANT to get it. Denying reality while pretending to be scientific should be subject to criminal penalties.

Read the code killers and get educated. You are a danger to your family.
http://acehoffman.org/

Avatar of:

Posts: 0

February 18, 2012

Please get the science right. Radiation is radiation, either energetic photons or subatomic particles released by radioactive decay or by high energy collisions between atoms. They blast around like bullets until their energy is spent. Chemical mutagens and chemotheraputic agents AS USED HERE are toxins that can hang around and may function for a long time. They either react with DNA causing direct mutagenesis, or interfere with DNA replication or cell division,  causing their own more or less specific range of cell death or genetic damage. Lumping them all together is not only wrong in language, it is not a good way to uncover the mechanism or mechanisms producing effects in offspring. The differences between agenbts will be the best clue to uncovering mechanism.

Do they all have the same effect? Unlikely! How long do chemotheraputic agents stay in cells at tiny concentrations, doing a little damage in the very large amount of DNA? It can take months for molecules of general anesthetics to diffuse out of the patient after an operation, although the effects become insignificant to a casual observer in a few days. Presumably there is some persistant chemical reaction in these mice too.

Avatar of:

Posts: 0

February 18, 2012

Please get the science right. Radiation is radiation, either energetic photons or subatomic particles released by radioactive decay or by high energy collisions between atoms. They blast around like bullets until their energy is spent. Chemical mutagens and chemotheraputic agents AS USED HERE are toxins that can hang around and may function for a long time. They either react with DNA causing direct mutagenesis, or interfere with DNA replication or cell division,  causing their own more or less specific range of cell death or genetic damage. Lumping them all together is not only wrong in language, it is not a good way to uncover the mechanism or mechanisms producing effects in offspring. The differences between agenbts will be the best clue to uncovering mechanism.

Do they all have the same effect? Unlikely! How long do chemotheraputic agents stay in cells at tiny concentrations, doing a little damage in the very large amount of DNA? It can take months for molecules of general anesthetics to diffuse out of the patient after an operation, although the effects become insignificant to a casual observer in a few days. Presumably there is some persistant chemical reaction in these mice too.

Avatar of: HFletcher_679

HFletcher_679

Posts: 44

February 18, 2012

Please get the science right. Radiation is radiation, either energetic photons or subatomic particles released by radioactive decay or by high energy collisions between atoms. They blast around like bullets until their energy is spent. Chemical mutagens and chemotheraputic agents AS USED HERE are toxins that can hang around and may function for a long time. They either react with DNA causing direct mutagenesis, or interfere with DNA replication or cell division,  causing their own more or less specific range of cell death or genetic damage. Lumping them all together is not only wrong in language, it is not a good way to uncover the mechanism or mechanisms producing effects in offspring. The differences between agenbts will be the best clue to uncovering mechanism.

Do they all have the same effect? Unlikely! How long do chemotheraputic agents stay in cells at tiny concentrations, doing a little damage in the very large amount of DNA? It can take months for molecules of general anesthetics to diffuse out of the patient after an operation, although the effects become insignificant to a casual observer in a few days. Presumably there is some persistant chemical reaction in these mice too.

Avatar of: Roy Niles

Roy Niles

Posts: 32

March 15, 2012

Cancel.

Avatar of:

Posts: 0

March 15, 2012

Cancel.

Avatar of:

Posts: 0

March 15, 2012

Cancel.

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