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Persistence of X-Ray-induced Chromosomal Rearrangements in Long-Term Cultures of Human Diploid Fibroblasts¹

Laboratory of Radiobiology, Harvard School of Public Health, Boston, Massachusetts 02115

As part of a long-term study of mechanisms of human cell neoplastic transformation, we have examined the change in the frequencies of X-ray-induced chromosome rearrangements in density-inhibited human foreskin fibroblasts as a function of subculture time. In nonproliferating cells, the frequency of chromosomal aberrations declined within 24 to 48 hr but still remained at a relatively high level up to 43 days after irradiation. Aberrations disappeared rapidly, however, when the cells were allowed to proliferate, indicating that these lesions are lethal to dividing cells. The frequency of induced translocations, as determined by analysis of G-banded karyotypes, was dose dependent and remained stable up to 20 mean population doublings after irradiation. When subculture of density-inhibited cultures was delayed for 4 hr after irradiation (confluent holding), the frequency of chromosomal aberrations in the first mitosis declined, whereas the translocation frequencies at later passage were elevated as compared with cells subcultured immediately. This correlates with the reported increase in the frequency of transformation under similar conditions. These findings support the hypothesis that chromosomal rearrangements induced by DNA damage may be involved in the initiation of cancer.

¹ Supported by Research Grant CA-11751 and Center Grant ES-00002 from the United States NIH.

² To whom requests for reprints should be addressed.

Received 2/22/84. Accepted 5/31/84.

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