title: Resistance to 1-Beta-d-arabinofuranosylcytosine and hypersensitivity to bleomycin in ataxia-telangiectasia B-lymphoblastoid cell-lines.
abstract: Three ataxia telangiectasia (AT) B-lymphoblastoid cell lines (B-LCLs) were examined for the chromosome aberrations induced by a DNA replication and repair inhibitor, 1-beta-D-arabinofuranosylcytosine (ara-C), and the effects of ara-C on the frequencies of chromosome aberrations caused by bleomycin (BLM). All these AT cell lines exhibited resistance to ara-C compared with normal and Bloom syndrome (BS) cells. In contrast with normal and BS cells, ara-C did not enhance chromosome aberrations produced by BLM in AT cells, although these cells showed hypersensitivity to BLM. After treatment with 1 X 10(-5) M ara-C for 24 h, total frequencies of chromosome aberrations in AT cells were 0.095-0.115/cell, which is about 6 times lower than those in normal (0.625/cell) and BS cells (0.775/cell). Following combination treatment with tetrahydrouridine (THU) and ara-C, we found that the frequencies of chromosome aberrations in AT B-LCLs were greatly increased compared with treatment with ara-C alone. Furthermore, when AT cells were pretreated with THU in combination with ara-C, then treated with BLM, a great synergistic enhancement of chromosome aberrations was observed. Because THU is an exclusive inhibitor of cytidine deaminase, these results strongly indicate that in AT B-LCLs there could be overproduction of cytidine Jeaminase, which is responsible for ara-C resistance. On the other hand, combination of THU and deoxycytidine (dCyd) significantly reduced chromosome aberrations induced by BLM in AT cells, although dCyd alone had no effect on bleomycin-induced chromosome aberrations. Break point distributions on chromosome bands following treatment with BLM or ara-C plus THU, alone or in combination, were examined and are discussed.
authors.affiliation: KOCHI MED SCH,DEPT ANAT,TUMOR CELL BIOL LAB,NANKOKU 783,JAPAN.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Shiraishi