Heterogeneity in chromosome damage and repair rates after bleomycin in ataxia telangiectasia cells

Abstract

Cells derived from patients with ataxia telangiectasia (AT) are known to be exceptionally sensitive to ionizing radiation and chemotherapeutic agents such as bleomycin (BLM), neocarzinostatin, and etoposide. This increased sensitivity is manifested by high chromosome aberration frequencies after treatment. In order to probe the underlying basis for this phenomenon, the technique of premature chromosome condensation was used to determine whether the increased chromosome damage observed after bleomycin treatment is due to increased initial chromosome damage or to a decreased capability of these cells to repair chromosome damage. Five AT cell lines were brought to quiescence and treated with BLM, and initial chromosome damage and repair rates were determined in the G1 prematurely condensed chromosomes. AT cells exhibited increased aberration frequencies compared to normal human fibroblasts immediately after BLM treatment. The five AT cell lines were heterogeneous in the fast component of chromosome break repair, varying from a nearly normal fast repair component in one cell line to a nearly defunct fast repair component in two other AT cell lines. Thus, while the AT cell lines were heterogeneous in the basis for their chromosome breakage sensitivity, all AT cell lines tested showed increased residual chromosome damage after BLM treatment while still in the quiescent phase.