Transformation of Epstein-Barr virus immortalized human B-cells by chemical carcinogens.

Epstein-Barr virus-immortalized human lymphocytes were used to analyze the transition from the benign hyperproliferative to the malignant transformed state. Treatment with N-acetoxy-2-acetylaminofluorene, a potent frameshift mutagen, induced conversion of the Epstein-Barr virus immortalized lymphocytes into high-grade "immunoblastic lymphomas" on injection into athymic mice, whereas injection of the untreated, original cells did not. The tumor cells were all of the B-cell lineage as determined by the presence of surface immunoglobulins and antigens detected by B-cell specific antibodies to B1 and B4, and the absence of the T-cell-specific markers, 3A1 and LEU-1. The N-acetoxy-2-acetylaminofluorene-induced tumor lines displayed abnormal diploid to tetraploid karyotypes. The fewest chromosomal rearrangement, excluding tetraploidy, observed in these chemically induced lymphomas involved a deletion in chromosome 6, and additions on both chromosomes 16 and 4. Neither major rearrangements nor amplifications were found for K-ras, H-ras, N-ras, c-myc, Blym, and c-myb in these tumor lines.