1993 Fiscal Year Final Research Report Summary
Detection of Pt (1R, 2R-diaminocyclohexane) bound to DNA in Cancer Cell by Monoclonal Antibody
| Project/Area Number |
04671336
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Fukuyama University |
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Principal Investigator |
HIROSE Junzo Fukuyama University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (70080215)
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| 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)
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| Project Period (FY) |
1992 – 1993
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| Keywords | monoclonal antibody / antitumor drug / platinum complex |
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| 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.
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