Chromothripsis in Hepatocarcinogenesis: The Role of a Micronuclear Aberration and Polyploidy

Abstract

In this study, we used the mouse model of chemically induced hepatocarcinogenesis to investigate the chromosomal aberrations in hepatic cells. The model was obtained by combined treatment of mice with Dipin (radiomimetic drug) followed by partial hepatectomy. Cytological analysis of isolated liver cells treated with Dipin has demonstrated a number of hepatocytes with structural nuclear abnormalities and multiple micronuclei. Karyotype analysis of polyploid hepatocytes has shown numerous chromosomal aberrations including alleged morphological manifestations of chromothripsis, a special type of genomic reorganization characterized by the local disintegration of chromosomes. Micronuclei with chromosomal fragments have developed as a result of double-strand DNA breaks and might serve as the initial substrate for chromothripsis. The emergence of micronuclei containing chromosomal fragments is the most important result of the treatment employed. Therefore, the presented model of liver cancer (hepatocarcinogenesis) can be used to study the process of chromothripsis in the future.