Chromosome and gene rearrangements in immortalized human lymphocytes infected with human T-lymphotropic virus type I.

Karyotypes of 26 human lymphocyte cultures, infected or noninfected with human T-lymphotropic virus type I (HTLV-I), with or without Epstein-Barr virus infection, were analyzed by G-banding. Hypodiploidy and structural abnormalities were seen more frequently in HTLV-I-infected cultures (30%) than in virus noninfected cultures (10%) propagated for less than 200 days. In all of six immortalized cell lines infected with HTLV-I alone or with both HTLV-I and Epstein-Barr virus, clonal chromosomal abnormalities characteristic for each cell line were observed in nearly 100% of cells examined after prolonged propagation. HTLV-I-infected interleukin 2-dependent T-cells acquired the ability to grow interleukin 2 independently after consecutive treatments with N-methyl-N'-nitro-N-nitrosoguanidine, 4-phorbol-12-myristate-13-acetate, and 1,2-benzopyrene. By Southern blot analysis of one T-cell line and three B-cell lines infected with HTLV-I alone or with HTLV-I and Epstein-Barr virus, rearrangements of the Jk gene were found in all B-cell lines, and rearrangements of the T-cell receptor beta gene were found in all cell lines regardless of their lineage. These results suggest that human lymphocytes undergo chromosome and gene rearrangements probably through an abnormal mitotic process caused by integration of HTLV-I proviral DNA, leading to the emergence of advantageous clones for growth. This process might be promoted synergetically by certain carcinogenic compounds present in the environment of HTLV-I-infected cells.