DNA DAMAGE BY ALKYLATING AGENTS AND THEIR REPAIR IN HUMAN TUMOR CELLS

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It has been shown that approximately 20% of human tumor lines and viral transformed lines are hypersensitive to alkylating agents due to an apparent absence of Alkylguanine Alkyltransferase. We have been able to partially purify the enzyme from human liver. This enzyme removes alkylation damage at the 06 position of guanine but not at other sites in DNA. We plan to further characterize this enzyme and purify it to the point where amino acid sequence information can be obtained. In collaberation with D. Yarosh, human liver extracts are being used to isolate adequate quantities of this protein. Differences in the transcription of specific RNA's in mer plus and mer minus cells are also being investigated.