Abstract
Carcinogenesis is a multistep process by which a normal cell gradually develops into a transformed malignant cell. The presence of structural and numerical chromosomal aberrations in tumour cells suggests that chromosomal instability (CIN) plays and important role in carcinogenesis. Numerous investigations have demonstrated that ionizing radiation is able to induce CIN. Research aimed to elucidate the precise role of ionizing radiation induced CIN in carcinogenesis requires methods capable to measure true CIN, i.e. the continuous formation of de novo chromosomal abnormalities. In a pilot study, we have successfully established a novel method to detect and quantify CIN within in situ fixated colonies of human epithelial cells. This strategy allows to visualize the occurrence of CIN within a colony (the progeny of a single cell) and to quantify the rate of CIN as events per number of cell generations. Preliminary results suggest that CIN initiated by telomere dysfunctioning, might be involved in the immortalization of these cells. More details of the colony based in situ fixation method will be presented and our preliminary results discussed. [J Radiat Res 44:374 (2003)]