IMBALANCE OF MORPHOLOGICALLY ADDRESSED TELOPHASES REFLECTS INTERPHASEDNA ANEUPLOIDY IN TUMORIGENESIS

Chromosome division figures (CDFs) are quantitatively different from n ormal mitoses and represent a novel cytogenetic phenomenon. This inves tigation was focused on morphologically addressed bipolar telophases i n histologically defined human biopsies and in the tumour breast cell- line MDA231. Single cell nuclei were recorded by image microphotometry on inflamed and premalignant lesions of skin (49 cases), oral mucosa (43) and colon mucosa (46). DNA content and replication status were an alysed in interphase nuclei as well as in mitoses and in CDFs. In cont rast to inflamed lesions, premalignancies were characterised by pronou nced endoreplication, when the rate exceeding 5 c was greater than or equal to 10% in interphase nuclei. CDFs from the corresponding lesions showed an aberrant DNA content beyond 5 c even more frequently. DNA p rofiles of metaphases and telophases resembled those of prophases. The refore, the DNA content of corresponding telophase hemispheres was mea sured. Severe differences averaged 0.3 c in MDA231 and up to 0.5 c in premalignant lesions. The mean difference between two corresponding he mispheres was 0.39 +/- 0.09 c in Bowenoid keratosis (n = 31), 0.40 +/- 0.08 c in high-grade dysplasia of oral mucosa (n = 16) and 0.21 +/- 0 .03 c in high-grade dysplasia of colon adenoma (n = 65 telophases). As a control, the telophase difference was only 0.07 +/- 0.02 c (n = 23) in foetal liver and 0.06 +/- 0.01 c in 24 amnion cells. Thus, genomic instability and, in consequence, genomic imbalance can best be quanti fied from the DNA profiles of telophase CDFs and from the various DNA amounts in their hemispheres. A strong selection against telophases wa s observed in neoplasias developing DNA aneuploidy. Those aberrant tel ophases which escape selection are thought to enhance tumour progressi on.