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Selective Chromosomal Damage and Cytotoxicity of ¹²⁵I-labeled Monoclonal Antibody 17-1a in Human Cancer Cells¹

Department of Radiation Oncology, Hahnemann University School of Medicine, Philadelphia, Pennsylvania 19102 [D. V. W., D. L.]; Centocor, Malvern, Pennsylvania 19355 [J. A. M.]; and The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104 [Z. S.]

A monoclonal antibody, 17-1a, which reacts with antigen expressed in human colon cancers was radiolabeled in high specific activity with ¹²⁵I. The combination of the antibody and this radionuclide was observed to elicit specific cellular damage after being internalized into cells of the SW1116 human colon cancer cell line. The degree of internalization was quantitatively measured and found to increase over time to 49% after a 48-h incubation period. During this period, significant chromosome aberrations were observed in the SW1116 cell line due to the Auger electrons of ¹²⁵I. This damage was not observed using Na¹²⁵I, a nonimmunoreactive radiolabeled antibody, or cells which did not contain the requisite antigen. The number of chromosomal aberrations increased with increasing radioactive concentration of ¹²⁵I-17-1a. The nuclear damage resulted in specific cellular cytotoxicity and decreased cell survival of SW1116 cells exposed to various concentrations of ¹²⁵I-17-1a.

¹ This work was supported in part by grants from the W. W. Smith Charitable Trust and the Brady Cancer Research Institute.

² To whom requests for reprints should be addressed.

Received 11/14/88. Revised 1/25/89. Accepted 3/ 1/89.

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