There is a need for novel and effective prophylactic treatments and 
radioprotective materials to protect civilians and military personnel from 
ionizing radiation in contaminated environments. Melanin, a naturally occurring, 
ubiquitous pigment, has been shown to confer radioresistance, acting as a 
potential radioprotective agent. We have demonstrated that melanized 
Cryptococcus neoformans (CN) cells had improved survival post ionizing 
irradiation than non-melanized ones. The goal of this study was to identify 
morphological changes in melanized and non-melanized CN cells following 
irradiation with densely-ionizing deuterons and alpha particles relative to 
sparsely-ionizing gamma radiation. We observed significant differences between 
the melanized and non-melanized CN cellular ultrastructure following 
irradiation. Melanized CN cells were relatively resistant to mid and max-dose 
levels of alpha particles and deuterons irradiation. Following irradiation the 
capsule was stripped, but the cell wall was intact and structural integrity was 
maintained. At the maximum dose, cytoplasmic vacuolization, and mitochondrial 
swelling started to occur. In contrast, the non-melanized CN strain was 
sensitive to the mid-dose radiation. Non-melanized cells presented two 
morphologies: small condensed, and swollen, lacking structural integrity. This 
morphological investigation provides the first direct evidence of the 
radioprotective properties of melanin in CN cells subjected to high RBE and high 
LET ionizing radiation.