Background and Objective: Hybrid cells are made from fusion of two or more somatic cells. After formation chromosomes are located in one membrane . . So nucleic condition of each fused cell has changes and two genomes and chromosomes interact with each other. Locating the genes in new nucleic and cytoplasmic condition and great chromosomal rearrangement in these new formed cells can affect their chemotherapeutic drug sensitivity. In this study the effect of bleomycin sulfate (BML) on two hybridoma cell lines, F3B6 and HF2x653 was compared with two non-hybridoma WIL2 and NS1, their parent cells, focusing on chromosome aberrations in G1 phase of the cell cycle.   Materials and Methods: Four frozen cell lines, F3B6, NS1, HF2x653 and WIL2 were thawed and separately cultured in RPMI 1640 supplemented with 10-15 % FBS. Cells were treated with two concentrations of bleomycin sulfate (50 and 100 µg/ml) at G1 phase during logarithmic phase of growth. After harvesting, preparation of metaphase spreads and Gimsa staining, aberrant cells and chromosomal aberrations were scored.   Results: Results showed that aberrations induced in hybridoma cells are similar to those induced in their parent cell lines. Cells with more chromosomes, ie. F3B6 and NS1, had more chromosomal damages in comparison with cells having less chromosomes, Study of the abundance of damages in comparison with chromosomes confirms this result. Frequency of chromosomal aberrations in lieu of in two similar cells (NS1&F3B6) were alike and more than the other two ,WIL2 and HF2X653, Although sometimes hybrid cells showed more or less sensitivity than their parental cell lines, they also did not show dose-dependent response to bleomycin sulfate at G1 phase of the cell cycle.   Conclusion: Hybridoma cell lines studied in this study showed similar frequency of bleomycin induced chromosomal aberrations compared to one of the parent cell lines and had more or less chromosome aberrations (sensitivity) than the other parent.