Comparison on the genotoxic effects of nuclear vs cytoplasmic irradiation from the alteration of CD59 gene locus

Using microbeam to irradiate human-hamster hybrid AL cells with defined number of α particles in highly localized spatial region, the author showed that cytoplasmic irradiation induced very little toxicity. For example, the cell killing by 4α particle traversal through the cytoplasm was about 10%, and about 70% cells survived after their cytoplasm was irradiated with 32 α particles. In contrast, the survival fractions for nuclear irradiation at the same doses were 35% and less than 1% respectively. Mutation induction showed that while nuclear irradiation induced 3-4 fold more CD59- mutants than cytoplasmic irradiation at equivalent particle traversal, at an equi-toxic dose level of 90% survival, the latter exposure mode induced 3.3 fold mutants than nuclear irradiation. Moreover, using multiplex PCR to analyze five marker genes on chromosome 11 (WT, CAT, PTH, APO-Al and RAS), the results showed that the majority of mutants induced by cytoplasmic irradiation had retained all of the marker genes analyzed. By comparison, the proportion of mutants suffering loss of additional chromosomal markers increased with increasing number of particle traversal through nuclei