Enhancement of simian virus 40 transformation and integration by 4-nitroquinoline 1-oxide.

Pretreatment of animal cells with X-ray (4, 14, 18), thymidine analogs (19), and chemical carcinogens (2, 3, 9) increases the sensitivity of survivingcells to transformation by DNA-oncogenic viruses. The property that many of these agents share is the abifity to induce strand breaks in cellular DNA. If viral transformation is dependent upon integration of viral DNA into cellular DNA, then the enhancement of transformation may be mediated through facilitation of the integration of viral DNA at the breakpoints of cell DNA. We have tested this possibility in the nonpermissive SV4O ChH3 cell transformation system (1 1) in combination with the chemical carcinogen, 4NQO. 4NQO induces singleor double-strand scissions of mamma lian cell DNA, and the scissions produced by low concentra tions of 4NQO are completely rejoined after incubation of cells in medium without 4NQO (1). Enhancement of SV4O and simian adenovirus 7 transformation by 4NQO has been described in different cell systems including ChH (5 , 9 , 16). We have shown previously that SV4O DNA becomes integrated into the DNA of CMI cells at 15 to 20 hr p.i. (8). The conditions of SV4O infection, 4NQO treatment, and the assay of transformation have been described (5), as has been the procedure for hybridization of SV4O complementary RNA with cell DNA to measure the extent of viral DNA integration (8). Several experiments demonstrate that treat ment of CMI cells with 4NQO (0.4 @g/ml)2 hr before SV4O infection induces a 2to 8-fold increase in the transformation frequency (Table 1), as calculated according to previously published methods (3, 5, 10). At this concentration of 4NQO,