Non-accidental structural chromosome aberrations in established monkey B-lymphocyte cell lines

Abstract

Established primate lymphocyte cell lines obtained from tumour samples and from EBV-positive monkeys served us as the model system for studying the role of genetic factors and chromosomal abnormalities in malignization. The investigation of chromosome regions and genes involved in chromosomal aberrations leading to malignization in these lines was the aim of our work. Cytogenetic analysis was performed at different stages of cultivation in vitro. To determine the oncogenes and tumour suppressor genes located on aberrant chromosomes, data on mapping rhesus macaque genes, and high similarity of human and monkey karyotypes were used. We found that, in the line obtained from lymphomatous baboon tissue, the inactivation of tumour suppressor gene RB1 on chromosome 17 after chromosomal rearrangement is one of the most probable causes of in vivo malignization. Chromosomal aberrations at the region of oncogene c-Ki-ras and tumour suppressor gene TP53 change the proliferative status and differentiation in established cell lines obtained from healthy but EBV-seropositive primates. The other cause of malignization in these lines is an increase in expression of the oncogene c-myc caused by trisomy of chromosome 8 where c-myc is located. Structural aberrations in established primate cell lines affecting several chromosomal loci were identified as: (1) causing the proto-oncogene activation – the central event in the tumour clone occurrence, and (2) deactivating tumour suppressor genes. The change in the chromosome number leads to increase in oncogenic products and to damage of regulatory functions associated with cell proliferation.