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Elevated frequencies of spontaneous chromosome breakage and hypersensitivity to radiation induced chromosome damage are characteristic findings in cultured lymphocytes and skin fibroblasts of patients with ataxia telangiectasia (AT). To determine whether long-term AT lymphoblastoid cells (B-lymphocytes) which do not express spontaneous chromosomal instability, exhibit increased chromosomal radiation sensitivity, four AT lymphoblastoid cell lines were exposed to various doses of 250 kVp X-rays during G2. At doses of 25 and 50 rad, the AT cells exhibited a 2–3 fold increase in radiation damage relative to that observed in B-cell lines or PHA stimulated lymphocytes from normal donors, while at 100 rad, the AT cells demonstrated approximately 1.5 times more lesions. These findings suggest that the genetic (or other) factors responsible for increased chromosomal radiation sensitivity in AT lymphocytes and fibroblasts also operate in long-term lymphoblastoid AT cells.

The chemotherapeutic agent cis-platinum(II)diamminedichloride (cis-PDD) has been shown to be mutagenic, teratogenic, and carcinogenic. We determined the cytogenetic effects of cis-PDD on human and rabbit lymphocytes in vitro and on rabbit marrow cells, lymph node cells, and lymphocytes in vivo. Lymphocyte cultures from two humans and one rabbit were treated in vitro with cis-PDD. For in vivo studies, five New Zealand white rabbits were given iv injections of cis-PDD. Posttreatment blood samples were withdrawn for analysis and rabbits were sacrificed at either 6 or 24 hr for cytogenetic analysis of marrow and node cells. Sister chromatid exchange (SCE) analysis of human and rabbit metaphases from lymphocytes treated in vitro showed that rabbit lymphocytes are more sensitive to SCE induction by cis-PDD. Significant increases in SCE were observed in lymphocyte cultures obtained as early as 1 hr post treatment from injected rabbits. Analysis of node, marrow, and lymphocyte metaphases from injected rabbits showed a high number of chromosome aberrations in these cells with bone marrow showing a delayed response to treatment. These results indicate that cis-PDD is clastogenic in hematopoietic tissues in vivo and that SCE methodology may be useful in monitoring patients receiving cis-PDD therapy.