Hyper-radiosensitivity affects low-dose acute myeloid leukemia incidence in a mathematical model.
Radiat Environ Biophys
; 61(3): 361-373, 2022 08.
Article
en En
| MEDLINE
| ID: mdl-35864346
ABSTRACT
In vitro experiments show that the cells possibly responsible for radiation-induced acute myeloid leukemia (rAML) exhibit low-dose hyper-radiosensitivity (HRS). In these cells, HRS is responsible for excess cell killing at low doses. Besides the endpoint of cell killing, HRS has also been shown to stimulate the low-dose formation of chromosomal aberrations such as deletions. Although HRS has been investigated extensively, little is known about the possible effect of HRS on low-dose cancer risk. In CBA mice, rAML can largely be explained in terms of a radiation-induced Sfpi1 deletion and a point mutation in the remaining Sfpi1 gene copy. The aim of this paper is to present and quantify possible mechanisms through which HRS may influence low-dose rAML incidence in CBA mice. To accomplish this, a mechanistic rAML CBA mouse model was developed to study HRS-dependent AML onset after low-dose photon irradiation. The rAML incidence was computed under the assumptions that target cells (1) do not exhibit HRS; (2) HRS only stimulates cell killing; or (3) HRS stimulates cell killing and the formation of the Sfpi1 deletion. In absence of HRS (control), the rAML dose-response curve can be approximated with a linear-quadratic function of the absorbed dose. Compared to the control, the assumption that HRS stimulates cell killing lowered the rAML incidence, whereas increased incidence was observed at low doses if HRS additionally stimulates the induction of the Sfpi1 deletion. In conclusion, cellular HRS affects the number of surviving pre-leukemic cells with an Sfpi1 deletion which, depending on the HRS assumption, directly translates to a lower/higher probability of developing rAML. Low-dose HRS may affect cancer risk in general by altering the probability that certain mutations occur/persist.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Leucemia Inducida por Radiación
Tipo de estudio:
Incidence_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Radiat Environ Biophys
Año:
2022
Tipo del documento:
Article
País de afiliación:
Países Bajos