On the mechanics of chromosomal aberrations: a study with single and multiple spatially-associated protons.

A unique radiation configuration, triads of protons, where mean separation between protons was controlled to be about 0.2 microns, has been used to irradiate Chinese hamster V79 cells. These triads of accelerated particles were more effective at producing chromosomal aberrations than randomly incident particles. Cells were irradiated with either single or three associated protons, with each proton depositing energy intracellularly at an LET of about 30 keV per micron. The associated protons were produced from accelerated molecular ions (H3+) that dissociated into atomic ions in a 6 mu Mylar foil on which the cells were growing, becoming triads of particles separated by a mean of about 0.2 microns in the cell nuclei. Chromosomal aberrations were scored from cells accumulated with colcemid over hourly intervals after irradiation. Those cells closest to mitosis (late G2) were the most sensitive to radiation, while overall "triple" protons were 52% more effective than single protons in producing aberrations. Only 10% of particles incident in nuclei resulted in an effect for the most sensitive period (late G2) dropping to 2% for the least sensitive period (early S--late G1). The frequencies of chromatid deletions declined dramatically with time post-irradiation, with isochromatid deletions less so and the frequencies of chromatid interchanges comparatively unchanged. Chromatid deletions and isochromatid deletions were often subtantially increased after "triple" proton irradiation, with the frequencies of chromatid interchanges less effected. This implies that both chromatid and isochromatid deletions can readily result from interactions between pairs of induced lesions about 0.2 microns apart. Achromatic lesions (gaps) were numerically equivalent after both irradiations implying a single lesion production mode. Results are compatible with there being a substantial short range component of interaction (less than 0.1 microns) between damaged sites, with a long range component of interaction extending to a few tenths of a micrometer.