What are the two main theories of biologic damage caused by ionizing radiation?

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Ionizing radiation causes biological damage mainly through two pathways. The direct pathway involves energy from the radiation hitting critical molecules itself—most notably DNA—causing ionizations that lead to breaks and other lesions. The indirect pathway arises when radiation interacts with water in the cell to produce reactive free radicals, such as hydroxyl radicals and hydrogen atoms. These radicals then diffuse and attack DNA and other cellular components, producing damage even though the radiation didn’t hit those targets directly.

In practice, indirect damage tends to dominate at low linear energy transfer (LET) because cells are rich in water, making radical formation common. At higher LET, the energy is deposited more densely along the track, increasing direct hits to DNA. The other proposed theories don’t align with the established mechanisms of radiation biology, which revolve around direct interactions with target molecules and indirect damage via water radiolysis.