| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Hiroyuki Fukuyama University, Faculty of Engineering, Research Assistant, 工学部, 助手 (90213321)
HIROMI Keitaro Fukuyama University, Faculty of Engineering, Professor, 工学部, 教授 (50025425)
|
|---|
| Budget Amount *help |
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
|
|---|
| Research Abstract |
Murine monoclonal antibodies that bind selectively to adducts formed on DNA by the antitumor drug Pt (1R, 2R-diarminocyclohexane) Cl_2 Pt (1R, 2R-dach), were elicited by immunization with calf thymus DNA modified with Pt (1R, 2R-dach)Cl_2 at the ratio of bound platinum per nucleotide of 0.075. The binding of monoclonal antibody to Pt (1R, 2R-dach) -modified DNA was competitively inhibited (50% control) in an enzyme-linked immunosorbent assay (ELISA) by 147 nM concentrations of Pt (1R, 2R-dach) bound to DNA.Slightly larger concentrations (272 nM) of Pt (1R, 2S-dach) modified DNA also inhibited antibody binding, where- as higher concentrations (2450 nM) of cis-Pt (NH_3)_2-DNA adduct were required for inhibition. DNA did not inhibit antibody binding to Pt (1R, 2R-dach) -DNA.The inactive platinum complex, trans-Pt (NH_3)_2-DNA did not form antibody-detectable adducts on DNA.Therefore, monoclonal antibody recognized a bifunctional Pt-DNA adduct. The platinum complexes (Pt (1R, 2R-dach) -DNA, Pt (1R, 2S-dach) -DNA) which have cyclohexane ring has higher activities than cis-Pt (NH_3)_2-DNA.This behavior implies that the antibody recognizes the cyclohexan ring moiety of the antigen.
|
