There is rapidly increasing information on the issue of three-dimensional nuclear architecture, according to which chromosomes are organized in localized territories and chromosome arms in exclusive domains within a given territory. The aim of the present study was to investigate the impact of different cell exposure conditions on cytogenetic damage induced by high-LET radiation. To this end the yield ratio of dicentrics to centric rings (F value) induced by ²⁴¹Am α particles was analyzed in monolayer cultures of human lymphocytes that were either settled or attached to foils, simulating a rounded or spread out cellular geometry, respectively. Monolayers were exposed in special irradiation chambers to 0.1 and 1.0 Gy and subsequently analyzed for chromosome aberrations. Independent of these different dose levels, significantly different F values of 10.07 ± 1.73 and 4.27 ± 0.44 have been determined in attached and settled lymphocytes, respectively. Since the diameter of nuclei vertically traversed by α particles in attached cells is about one-half that in settled cells, these F values support the postulate that proximity effects regarding the chromatin geometry in flattened or spherical human lymphocytes influence the formation of high-LET radiation-induced dicentrics and centric rings. A comparison with our earlier data sets obtained for both in vitro and in vivo exposure of human lymphocytes to α particles or ¹³⁷Cs γ rays supports the notion that the F value depends on the radiation quality when investigations are confined to spherical human lymphocytes. Thus the F value should not be ruled out as a practical chromosomal “fingerprint” for past exposure to high-LET radiation.