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Target-cell hypothesis
Late effect was a direct consequence of cell killing
BUT new provocative knowledge appeared
Bystander effect
Evidence that targeted cytoplasmic irradiation results in mutation in
the nucleus of the hit cells and that cells that are
not
directly hit by
an alpha particle, whether nuclear or cytoplasm, but in the vicinity of
one that does, contribute to the genotoxic response of the cell
population
The hypothesis was based on
in vitro
radiosensitivity, but large studies
could not show a correlation between
in vitro
radiosensitivity and clinical
response
How to explain fibrosis? Fibrotic tissue is dominated by excessive collagen
deposition. How can killing of fibroblasts lead to increased collagen
production?
Clinical studies showed that non-cytotoxic drugs as Tamoxifen could
increase the incidence of late radiation-induced fibrosis, so other
mechanisms must be in play