Radiation therapy - necrosis or apoptosis?

[Phloston]

I had read somewhere a while ago that radiation therapy induces cell death via free radical formation, not because of mutations caused to DNA.

Would the cells recognize the damage and apoptose, or do they undergo necrosis?

Could someone please explain + give a mechanism?

My follow-up question would be if this is similar to free radical formation secondary to re-perfusion injury, such as that associated with post-MI myocardium; this produces coagulative necrosis.

Is there a similarity between the former and latter?

Cheers,

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[tzmd]

According to Goljan RR, radiation causes pathologic apoptosis due to DNA damage. It does not mention though if the damage to the DNA is by mutation or free radical formation. Since it is apoptosis and not necrosis, it doesn't correlate with the reperfusion injury example you mentioned.

 

[Dallas]

I had read somewhere a while ago that radiation therapy induces cell death via free radical formation, not because of mutations caused to DNA.

Would the cells recognize the damage and apoptose, or do they undergo necrosis?

Could someone please explain + give a mechanism?

My follow-up question would be if this is similar to free radical formation secondary to re-perfusion injury, such as that associated with post-MI myocardium; this produces coagulative necrosis.

Is there a similarity between the former and latter?

Cheers,

My gut feeling would say it depends on the extent of radiation.
Remember, the radiation we are talking about is the ionizing kind of radiation. So as it passes through your cell it will push electrons off of molecules and in that manner create free radicals. Your cell however is equipped with antioxidants and protective mechanisms so I would say it depends on the dose and extent of damage.

In general however I expect it to be apoptosis since the mechanism in typical cases is through DNA problems and induced apoptosis due to irreparable damage. I've never heard of a gamma knife causing liquifactive necrosis in the brain for example. Or caseous necrosis in the prostate when they radiate the tumors.

The mechanism of necrosis in MI and reperfusion injury is not caused by free radicals. Its caused by hypoxia, the repferusion injury creates free radicals which just enhances/intensifies the damage necrosing cells are already exposed to. The necrosis is thus not initiated or maintained by free radicals, but hypoxia.

 

[Phloston]

My gut feeling would say it depends on the extent of radiation.
Remember, the radiation we are talking about is the ionizing kind of radiation. So as it passes through your cell it will push electrons off of molecules and in that manner create free radicals. Your cell however is equipped with antioxidants and protective mechanisms so I would say it depends on the dose and extent of damage.

In general however I expect it to be apoptosis since the mechanism in typical cases is through DNA problems and induced apoptosis due to irreparable damage. I've never heard of a gamma knife causing liquifactive necrosis in the brain for example. Or caseous necrosis in the prostate when they radiate the tumors.

The mechanism of necrosis in MI and reperfusion injury is not caused by free radicals. Its caused by hypoxia, the repferusion injury creates free radicals which just enhances/intensifies the damage necrosing cells are already exposed to. The necrosis is thus not initiated or maintained by free radicals, but hypoxia.

Your last mini-paragraph sounds good, but I want a little more explanation. The "necrosing cells" are penumbric, meaning they're technically able to survive if oxygen + ATP are restored. Necrosis, however, is an irreversible process. So the free radicals created by re-perfusion must initiate the process. At least that's my reasoning.

 

[Dallas]

Your last mini-paragraph sounds good, but I want a little more explanation. The "necrosing cells" are penumbric, meaning they're technically able to survive if oxygen + ATP are restored. Necrosis, however, is an irreversible process. So the free radicals created by re-perfusion must initiate the process. At least that's my reasoning.

Well necrosis is rather a process of the cell trying to hang in there as long as possible before irreversible damage occurs. Such as nuclear fragmentation, mitochondrial vacuolization or plasmalemma disruption. These are irreversible injuries from which the cell cannot recover.

Free radicals may be the factor that kicks the reversibly suffering cells over the edge into irreversible country.

However, in radiation this is more due to the checks and balances in DNA repair and internal signaling for apoptosis, not the same mechanism as free radical damage to mitochondra, plasmalemma. However nucleus can be argued if its the same, that is if free radicals from reperfusion do injure DNA.

 

[ijn]

I'd agree that normal cells hit with radiation will undergo apoptosis assuming the apoptosis genes haven't been damaged beyond recognition. But cancer cells tend to not give a **** how broken their DNA is and keep dividing until the cows come home. I'd lean more towards to necrosis if they're talking about a tumor.

 

[Charles_Carmichael]

Ionizing radiation (the type used in RT) causes significant DNA damage, the most critical (and lethal) lesion being double-strand breaks. There's a fair bit of evidence linking the incidence of DNA DSBs to extent of cell killing via RT. Whether a cell survives and continues to be able to divide or not depends on the extent of the damage and how robust its DNA repair mechanisms are. There are both direct (where secondary electrons damage DNA) and indirect (via hydroxyl radicals produced by interaction of water with secondary electrons) actions through which IR damages DNA.

The dominant mode of death after RT is called mitotic death (aka. mitotic catastrophe) -- death occurs while the irradiated cells are trying to divide due to aberrant mitosis. But this doesn't mean that it's the only form of death that IR induces. IR also activates the intrinsic apoptosis pathway via p53 or acid sphingomyelinase/ceramide (due to membrane damage from RT), for example. IR can also induce necrosis (though mitotic catastrophe and apoptosis, I think, still predominate).