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Repair of 06-alkylguanine during DNA synthesis in murine bone marrow haematopoietic precursors

By Stanton L. Gerson, Joan E. Trey, Kathleen Miller, Et Al, Contact The Aacr Publications, Hematopoietic Precursors, Stanton L. Gerson, Joan E. Trey, Kathleen Miller and Evan Benjamin


O'-AIkylguanine, a DNA adduci formed by nitrosoureas, becomes the site of a point mutation during DNA synthesis by preferentially base mispairing with thymine rather than correctly base pairing with cytosine. To repair this adduct, cells contain a limited amount of 06-alkylguanine-DNA alkyltransferase (alkyltransferase), a protein which removes the alkyl group in a stoichiometric reaction. To prevent mutations, repair must occur before DNA replication takes place. Consequently, formation of point mutations is related inversely to the number of alkyltransferase molecules and directly to the rate of DNA synthesis. Bone marrow hematopoietic precursors, the target for nitrosourea-induced leukemia, are deficient in alkyltransferase activity. We questioned whether regen erating bone marrow is more susceptible to nitrosoureas than other organs due to persistently low levels of alkyltransferase activity during periods of increased cell proliferation and DNA synthesis. Following syngenei

Year: 1987
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