Effect of the diaminocyclohexane carrier ligand on platinum adduct formation, repair, and lethality

Journal Article · Tue Jan 30 04:00:00 EST 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00456a026· OSTI ID:6693384

Page, J D; Husain, I; Sancar, A; Chaney, S G ^[1]

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1. Univ. of North Carolina, Chapel Hill (USA)

Platinum compounds with the diaminocyclohexane (dach) carrier ligand are of particular interest because cell lines that have developed resistance to platinum compounds in general often retain sensitivity to dach-platinum compounds, suggesting that the dach carrier ligand affects the formation, repair, or lethality of platinum-DNA adducts. The effect of the dach ligand on platinum adduct formation was assessed by using the (HaeIII-HindIII){sub 146} fragment of pBR322 treated to give equal amounts of dach- or ethylene-diamine-platinum adducts. The sites of adduct formation were mapped by digestion with Escherichia coli ABC excinuclease. There were no significant effects of the dach carrier ligand on the types or sites of platinum adduct formation. The effect of the dach ligand on platinum adduct repair was determined by using synthetic oligomers designed to have single, specific platinum adducts. These data suggest that if the carrier ligand has any effect on the repair of platinum adducts, it is more likely to exert that effect on the repair of platinum monoadducts or GNG diadducts rather than on the more abundant AG or GG diadducts. ({sup 14}C)Thiourea incorporation was used to quantitate the rate of monoadduct to diadduct conversion. Finally, the effect of the dach ligand on platinum adduct lethality was assessed by determining the effect of dach- and en-platinum adducts on the transformation efficiency of pBR322 into a repair-deficient (recA{sup {minus}} uvrA{sup {minus}}) strain of E. coli. These data suggest that the dach carrier ligand can significantly affect the ability of platinum-DNA adducts to block essential processes such as replication and transcription.

• OSTI ID: 6693384
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:4; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ALKANES
ANTITHYROID DRUGS
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARBON 14 COMPOUNDS
CARBONIC ACID DERIVATIVES
CYCLOALKANES
CYCLOHEXANE
DNA ADDUCTS
DNA REPAIR
DRUGS
ENZYMES
ESCHERICHIA COLI
ESTERASES
HORMONE ANTAGONISTS
HYDROCARBONS
HYDROLASES
LABELLED COMPOUNDS
LIGANDS
MICROORGANISMS
NUCLEASES
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHODIESTERASES
PLATINUM COMPOUNDS
RECOVERY
REPAIR
THIOUREA
THIOUREAS
TRANSITION ELEMENT COMPOUNDS
UPTAKE