Conclusions
Although the incidence of malignancy is related to radiation quality, and increased due to loss of Mlh1, the phenotype of the tumors is independent of LET.
Purpose
Humans are exposed to charged particles in different scenarios. The use of protons and high-linear energy transfer (LET) in cancer treatment is steadily growing. In outer space, astronauts will be exposed to a mixed radiation field composed of both protons and heavy ions, in particularly the long-term space missions outside of earth's magnetosphere. Thus, understanding the radiobiology and transforming potential of these types of ionizing radiation are of paramount importance.
Results
We found that Mlh1 deficient animals are highly prone to develop lymphomas when exposed to either low doses of protons or 28Si ions. The lymphomas that develop are genetically indistinguishable, in spite of different types of damage elicited by low- and high-LET radiation. RNA sequencing analyses reveal similar gene expression patterns, similar numbers of altered genes, similar numbers of single nucleotide variants and insertions and deletions, and similar activation of known leukemogenic loci. Conclusions: Although the incidence of malignancy is related to radiation quality, and increased due to loss of Mlh1, the phenotype of the tumors is independent of LET.