Alphoid DNA nucleotide sequences from two human cell lines and the corresponding...

In order to study the interaction between cis-diamminedichloroplatinum(II) (CDDP) and representative human DNA in a highly defined manner, alphoid sequence DNA was isolated from two human parental cancer lines (one of head and neck squamous cell origin, SCC-25, and one of breast carcinoma origin, MCF-7) as well as from three CDDP-resistant cell lines derived from the parental lines. The alphoid DNAs were then cloned and tested for homology with published consensus sequence results. Percent homology with the consensus sequence varied between 84.4% and 91.7% for all of the cloned alphoid DNA tested and there was no significant difference for parentally derived versus resistant subline derived alphoid DNA. These results suggest, as expected, that resistance to the mutagenic chemotherapeutic drug CDDP is not the result of a general alteration in DNA base sequence from guanine and adenine to cytosine and thymidine, which are less favorable binding sites. The highly defined, abundant alphoid sequence DNA should provide an excellent model for investigating the interaction between various DNA active drugs and human DNA.