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Chemical reactivity of monofunctional platinum-DNA adducts

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00364a012· OSTI ID:6962464
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Complexes formed in vitro between cis- or trans-PtCl/sub 2/(NH/sub 3/)/sub 2/ (DDP) and DNA were found to contain monofunctional adducts that reacted with exogenous guanosine. (/sup 14/C)Guo bound irreversibly to cis- and trans-DDP-DNA complexes to form bis-Gua adducts. The reaction was first order with respect to the concentration of both (/sup 14/C)Guo and platinum-DNA complex, but the rate of the reaction varied nonlinearly as a function of the level of platinum binding on DNA. The reaction between (/sup 14/C)Guo and these platinum-DNA complexes was used to probe the concentration and stability of the monofunctional adducts and to investigate their chemistry in situ. The concentration of monofunctional adducts was highest immediately after reaction of DDP with DNA for 2 h at 37/sup 0/C, at which time they represented greater than 15% of the cis-DDP-DNA lesions and on the order of 80% of the trans-DDP-DNA lesions. The cis-DDP-DNA complex reacted with (/sup 14/C)Guo by two kinetically distinct processes, indicating two types of reactive adducts. The most reactive adduct represented 5% of the platinum lesions. These monofunctional adducts disappeared during the incubation of the platinum-DNA complexes in the absence of drug, probably as a result of chelation to DNA. The half-lives of this chelation at 37/sup 0/C, 10 mM NaClO/sub 4/, were 15 and 30 h for the cis and trans complexes, respectively. Monofunctional adducts were formed on Gua bases in DNA.
Research Organization:
Laboratoire de Pharmacologie et de Toxicologie Fondamentales, Toulouse, France
OSTI ID:
6962464
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 16; ISSN BICHA
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AROMATICS
AZAARENES
BIOCHEMICAL REACTION KINETICS
COMPLEXES
DNA ADDUCTS
ELEMENTS
GUANOSINE
HETEROCYCLIC COMPOUNDS
IN VITRO
KINETICS
METALS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PLATINUM
PLATINUM METALS
PURINES
REACTION KINETICS
RIBOSIDES
TRANSITION ELEMENTS