Application of a sensitive immunoassay to the study of DNA adducts formed in peripheral blood mononuclear cells of patients undergoing high-dose melphalan therapy.
The levels of DNA adducts formed in peripheral blood mononuclear cells of 13 patients undergoing high-dose melphalan therapy were determined 0-24 h after drug administration using a modification of a previously described immunoassay. This assay was validated for DNA extracted from drug-treated cells. Adduct levels in normal mononuclear blood cells 1 h after drug administration correlated well (r = 0.846) with drug dose (expressed as mg/m2) and with area under the curve for plasma levels of melphalan during the first h (r = 0.842). 1 patient sustained a high degree of toxic side-effects from the melphalan treatment and showed a high level of adducts. Plasma cell leukaemia tumour cells from another patient showed a level of adducts approximately six times higher than those in the normal blood cells of the other patients. The levels of DNA adducts in normal peripheral blood mononuclear cells did not change markedly between 1 and 24 h after drug administration.
Tilby
M J
MJ
Leukaemia Research Fund Unit, New Medical School, Newcastle University, Newcastle upon Tyne, U.K.
Newell
D R
DR
Viner
C
C
Selby
P J
PJ
Dean
C J
CJ
D000478:Alkylation; D003432:Cross-Linking Reagents / Q000493:pharmacokinetics; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007952:Leukemia, Plasma Cell / Q000188:drug therapy; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008558:Melphalan / Q000378:metabolism*; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy; D013997:Time Factors
D003432:Cross-Linking Reagents; D004247:DNA; D008558:Melphalan