Monoclonal antibodies to DNA modified with cis- or trans-diamminedichloroplatinum(II)

Journal Article · Tue Dec 01 04:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.23.8225· OSTI ID:6218523

Sundquist, W I; Lippard, S J; Stollar, B D

Murine monoclonal antibodies that bind selectively to adducts formed on DNA by the antitumor drug cis-diamminedichloroplatinum(II), cis-DDP, or to the chemothrapeutically inactive trans isomer trans-DDP were elicited by immunization with calf thymus DNA modified with either cis- or trans-DDP at ratios of bound platinum per nucleotide, (D/N)/sub b/, of 0.06-0.08. The binding of two monoclonal antibodies to cis-DDP-modified DNA was competitively inhibited in an enzyme-linked immunosorbent assay (ELISA) by 4-6 nM concentrations of cis-DDP bound to DNA. Adducts formed by cis-DDP on other synthetic DNA polymers did not inhibit antibody binding to cis-DDP-DNA. The biologically active compounds (Pt(en)Cl/sub 2/), (Pt(dach)Cl/sub 2/), and (Pt(NH/sub 3/)/sub 2/(cbdca)) (carboplatin) all formed antibody-detectable adducts on DNA, whereas the inactive platinum complexes trans-DDP and (Pt(dien)Cl)Cl (dien, diethylenetriamine) did not. The monoclonal antibodies therefore recognize a bifunctional Pt-DNA adduct with cis stereochemistry in which platinum is coordinated by two adjacent guanines or, to a lesser degree, by adjacent adenine and guanine. A monoclonal antibody raised against trans-DDP-DNA was competitively inhibited in an ELISA by 40 nM trans-DDP bound to DNA. This antibody crossreacted with unmodified, denatured DNA. The recognition of cis- or trans-DDP-modified DNAs by monoclonal antibodies thus parallels the known modes of DNA binding of these compounds and may correlate with their biological activities.

• Research Organization: Massachusetts Institute of Technology, Cambridge (USA)
• OSTI ID: 6218523
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:23; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADDUCTS
ANIMAL CELLS
ANIMALS
ANTIBODIES
BIOLOGICAL EFFECTS
CHEMICAL REACTIONS
CROSS-LINKING
DNA
DNA ADDUCTS
ENZYME IMMUNOASSAY
HYBRIDOMAS
IMMUNOASSAY
MAMMALS
MICE
MONOCLONAL ANTIBODIES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PLATINUM COMPOUNDS
POLYMERIZATION
RODENTS
STEREOCHEMISTRY
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES