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In vivo photoreaction of a chiral cobalt complex: DNA cleavage by Co(DIP)_3^(3+) in mammalian cells

Chapnick, Lowell B. and Chasin, Lawrence A. and Raphael, Adrienne L. and Barton, Jacqueline K. (1988) In vivo photoreaction of a chiral cobalt complex: DNA cleavage by Co(DIP)_3^(3+) in mammalian cells. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 201 (1). pp. 17-26. ISSN 0027-5107. http://resolver.caltech.edu/CaltechAUTHORS:20160513-104524679

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Abstract

The chiral complex tris (diphenylphenanthroline) cobalt (III) (Co(DIP)_3^(3+) provides a photoreactive probe for chromatin structure in mammalian cells. The complex, which upon photoactivation cleaves DNA in a conformation-specific fashion in vitro, is shown also to cleave DNA in vivo upon irradiation with ultraviolet light (>300 nm). Δ- and Λ-Co (DIP)_3^(3+) isomers are taken up efficiently into cultured Chinese hamster ovary cells and concentrate within cell nuclei. In the absence of light the complexes are toxic to the cells (10% survival at ∼ 300 nM), but after ultraviolet irradiation, the toxicity is markedly (>10-fold) increased. The synergism between irradiation and Co(DIP)_3^(3+) administration may lie in photoreactions with DNA elicited by the cobalt complex. Alkaline sucrose gradient of DNA from cells exposed to Λ-Co(DIP)_3^(3+) and irradiation show single-stranded DNA fragmentation under conditions where little cleavage is seen in cells either incubated with Λ-Co(DIP)_3^(3+) or irradiated with > 300 nm A ultraviolet light. Cellular DNA is cleaved with lower efficiency than naked DNA, likely due to decreased accessibility of sites in vivo. Hybridization of fragments obtained from the alkaline sucrose gradients to a probe specific for the amplified dihydrofolate reductase gene reveals a similar distribution of dhfr sequences and total DNA, indicating that the family of conformations recognized by Λ-Co(DIP)_3^(3+) are dispersed throughout the genome.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/0027-5107(88)90107-8DOIArticle
http://www.sciencedirect.com/science/article/pii/0027510788901078PublisherArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 1988 Elsevier Science Publishers B.V. Revision received 23 November 1987; Accepted 12 January 1988. This work has been generously supported by a grant (CHE85-9580) from the National Science Foundation.
Funders:
Funding AgencyGrant Number
NSFCHE85-9580
Subject Keywords:Cobalt complex, photoreaction in vivo; DNA cleavage; Mammalian cells, DNA cleavage; Chiral complex, Co(DIP)_3^(3+); Chromatin structure, mammalian cells
Record Number:CaltechAUTHORS:20160513-104524679
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20160513-104524679
Official Citation:Lowell B. Chapnick, Lawrence A. Chasin, Adrienne L. Raphael, Jacqueline K. Barton, In vivo photoreaction of a chiral cobalt complex: DNA cleavage by Co(DIP)33+ in mammalian cells, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Volume 201, Issue 1, September 1988, Pages 17-26, ISSN 0027-5107, http://dx.doi.org/10.1016/0027-5107(88)90107-8. (http://www.sciencedirect.com/science/article/pii/0027510788901078)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67074
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:13 May 2016 18:43
Last Modified:13 May 2016 18:43

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