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Genomic Rearrangements in Mouse C3H/10T Cells Transformed by X-Rays, UV-C, and 3-Methylcholanthrene, Detected by a DNA Fingerprint Assay¹

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

Genomic rearrangements occurring in C3H/10T cells transformed by X-rays were examined with a DNA fingerprint assay. Four multilocus and multiallele probes were employed (M, X, H10, and H16) that detect different families of minisatellite sequences dispersed throughout the genome. Genomic rearrangements were detectable only with probe M. This specificity may be explained by a genomic instability owing to a specific sequence or structure of DNA recognized by probe M. Genomic rearrangements were detected in 5 of 12 type III foci transformed by 600 cGy of X-rays and in all clones isolated from a previously transformed clone exposed to a second dose of 600 cGy and recloned. The latter data suggest that the stage of transformation and the occurrence of genomic rearrangement induced by X-rays may be related. An intensity shift or a complete deletion of band 2 was common to these X-ray-induced clones, as well as to clones transformed by UV-C (1 of 5) or 3-methylcholanthrene (4 of 6). This band did not hybridize to probes for the retinoblastoma gene RB or for p53. We hypothesize that the loss of band 2 may reflect a significant genetic change in the transformation of 10T cells, perhaps representing the inactivation of a tumor suppressor gene other than RB or p53. Additional rearrangements occurred in X-ray-transformed clones; these rearrangements were not observed with the other carcinogens. Aside from the changes in band 2, however, no specific pattern of genomic rearrangement was associated with X-ray transformation, and the presence or absence of rearrangements did not correlate with tumorigenicity in syngeneic nonimmunosuppressed C3H mice.

¹ This research was supported by Grants CA-47542 and ES-00002 from the NIH and a fellowship to B. P. from les Fonds de la Recherche en Sante du Quebec.

² To whom requests for reprints should be addressed, at Laboratory of Radiobiology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115.

Received 5/19/92. Accepted 8/ 8/92.

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