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Oxford University Press, Nucleic Acids Research, 1(23), p. 42-50, 1995

DOI: 10.1093/nar/23.1.42

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Stability of adriamycin-induced DNA adducts and interstrand crosslinks.

Journal article published in 1995 by Anne van Rosmalen, Carleen Cullinane, Suzanne M. Cutts ORCID, Don R. Phillips
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The stability of adriamycin-induced DNA adducts and interstrand crosslinks was measured at 37 degrees C by three independent procedures. The loss of [14C]-labelled adducts was described by two first-order decays with half-lives of 7.4 h (60% amplitude) and 39 h (40%). The loss of the drug chromophore also exhibited a biphasic character, with half-lives of 6 h (65%) and approximately 150 h (35%). The decay of transcriptional blockages at an isolated, apparent interstrand GpC crosslinking site was described by two first-order processes, with half-lives of 3 h (65%) and 40 h (35%), whereas the decay of transcriptional blockages at an isolated guanine residue (apparent site of monoadduct) was completely described by a first-order decay with a half-life of 5.3 h. The loss of interstrand crosslinks was measured using a gel electrophoresis assay, and the decay was characterised by a single first-order process with a half-life of 4.7 h. Collectively, these values serve to define a model of the interstrand crosslink with unstable sites of attachment at both ends of the crosslink, with half-lives at either end being approximately 5 and 40 h. The adducts exhibited increasing lability with increasing pH, and were particularly unstable at pH 12, with a half-life of approximately 0.5 h. The adducts were also heat labile, with an overall melting temperature of 67 degrees C (10 min exposure) and this was also the thermal lability measured at three individual adduct sites probed by lambda exonuclease.