Complementary directed modifications of nucleic acids and oncogene-directed mutagenesis in vivo

High reactivity of the polyalkylating ss oligomers that were sense or antisense 30-200-mers containing sequences complementary to E1 oncogenes of simian adenovirus SA7 and one alkylating residue -CH2CH2N(C2H5OH) (CH2)3N(Ph-p-CH2OH)CH2CH2Cl per each 25 bases of oligomers was demonstrated in vitro by alkylation of ss DNA of recombinant M 13 mp8E1 and mp9E1 phages with inserted E1 sequences of adenovirus oncogene and then by followed complete and selective elimination of E1 sequences from recombinant ss DNA. Treatment of rodent cell cultures transformed by oncogenic SA7 with polyalkylating oligomers which are complementary to the long region of the minus or plus chains of E1 DNA of SA7 revealed a rather high extent of mutant cell clones formation. The cells formed were normalized; they had lost some properties of the transformed cells. Dividing cell clones inherited the new phenotypic properties: morphology, slower and more limited proliferation, and higher dependence on bovine serum growth factors. Some of the mutant cell DNAs demonstrated different mutations in the E1A sequences of the integrated proviral oncogene. There were exchanges G to C (leu to val) in the 525 and C to A (asp to tyr) in the 555 positions of E1A oncogene. Besides a deletions in the 1057-1477 E1A region or/and a mutation in the 1457-1477 of E1A were observed. Thus the inherited cell normalization observed is performed due to oncogene-directed mutagenesis in vivo.