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

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R. S. Day, III, D. Yarosh, and others have 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. This enzyme removes alkylation damage at the 0-6 position of guanine but not at other sites in DNA. Dr. D. Yarosh in collaboration with our unit has been able to partially purify the enzyme from human liver and raise polyclonal antibodies to this protein. Studies have been initiated to develop monoclonal antibodies to this protein. With high affinity antibodies, we will be able to further purify this protein. With sufficient purification, partial amino acid sequence can be obtained and used to synthesize oligonucleotide probes which will be used to screen human liver cDNA libraries. Such antibodies can also be used to screen human liver cDNA expression libraries.