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Cellular Hypersensitivity to Neocarzinostatin in Ataxia-Telangiectasia Skin Fibroblasts¹

Departments of Human Genetics [Y. S.] and Molecular Virology [Y. S., E. T., Y. B.], The Hebrew University-Hadassah Medical Center, Jerusalem, Israel

Cellular sensitivity of human skin fibroblast strains from three healthy donors, eight ataxia-telangiectasia (A-T) patients belonging to six sibships, and two A-T heterozygotes to the lethal action of the antitumor antibiotic neocarzinostatin was tested, using colony-forming ability as the criterion for survival. All the A-T strains were significantly more sensitive to killing by neocarzinostatin than were the control strains. The average D_o for the A-T strains following neocarzinostatin treatment was 14.6 ng/ml, as compared to 37.9 ng/ml for the normal strains. The two A-T heterozygous strains showed intermediate sensitivity with an average D_o of 26.9 ng/ml.

Neocarzinostatin sensitivity of A-T cells could therefore serve as a convenient aid for the laboratory diagnosis of A-T. Since A-T cells are also known to be hypersensitive to ionizing radiation and bleomycin, it would appear that they are primarily hypersensitive to DNA-breaking agents.

¹ Supported by United States-Israel Binational Science Foundation Grant 79/1845.

² To whom requests for reprints should be addressed, at the Department of Molecular Virology, The Hebrew University-Hadassah Medical School, P. O. Box 1172, 91010 Jerusalem, Israel.

Received 11/ 4/81. Accepted 3/11/82.