MORPHOLOGICAL TRANSFORMATION OF 10T1/2 MOUSE EMBRYO CELLS CAN BE INITIATED BY DNA DOUBLE-STRAND BREAKS ALONE

Malignant transformation of mouse fibroblasts was produced by electroporation with restriction enzymes. Similar transformation frequencies were observed with Pstl, Pvull, and Xbal, which cut genomic DNA at similar overall frequencies but have different termini, i.e., a 3' overhang, a blunt end, and a 5' overhang, respectively. The dose-response curve for restriction enzyme transformation shows a marked plateau in frequencies of transformed foci per surviving cell, whereas x-irradiation of the same cells gives a linear dose-response curve. Evidently, transformation can be caused by DNA double-strand breaks alone at a limited number of sites, but the evidence from x rays suggests that other kinds of DNA damage can cause transformation independently.