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Title: Site specific cleavage of thetaX-174 replicative form DNA after modification by N-acetoxy-N-2-acetylaminofluorene

Journal Article · · Carcinogenesis (N.Y.); (United States)

Three kinds of structural disturbances were found in an 88 base pair (bp) fragment of thetaX-174 DNA after exposure to N-acetoxy-N-2-acetylaminofluorene (N-Aco-AAF). Frequent strand scissions at two specific guanine sites on the 5' /sup 32/P-end-labeled fragment were identified by base sequence analysis. Scissions at these two sites were induced at neutral pH and they were not increased by treatment with apurinic endonuclease. They are an immediate consequence of N-Aco-AAF action and are not primarily apurinic sites. Alkali treatment with 1 M piperidine at 90/sup 0/C induced strand scissions at every guanine, demonstrating adduct slices, depurination and strand scissions. Adducted DNA was sensitive to single-strand specific nuclease digestion, suggesting unwound DNA. These studies indicate the prediliction of N-Aco-AAF for certain DNA sites and they suggest three kinds of DNA modifications which can be expected after adduction by this carcinogen. Some of the sites may be premutational carcinogen-induced DNA structural modifications.

Research Organization:
Albert Einstein Coll. of Medicine, Bronx, NY
DOE Contract Number:
AC02-83ER60160
OSTI ID:
6830631
Journal Information:
Carcinogenesis (N.Y.); (United States), Vol. 4:11
Country of Publication:
United States
Language:
English