Determination of N7-methylguanine in DNA of white blood cells from cancer patients treated with dacarbazine.
An ELISA method was used to determine N7-methylguanine (N7-MeGua) adducts in DNA of white blood cells from cancer patients treated with the methylating antitumor drug dacarbazine by i.v. administration. From four patients who received dacarbazine only, at dosages of 250, 400 or 800 mg/m2, the blood samples were collected before and several days after administration, and from one patient also during the first few hours. N7-MeGua levels increased rapidly during the first hour after treatment, hardly changed during the following 7 h and decreased during the next days (half-life of approximately 72 h). The adduct levels appeared to be dose-dependent. Blood cells were also analyzed from three patients who received dacarbazine (225 mg/m2) in combination with other chemotherapeutic drugs during three successive days. One of these patients showed a larger initial level of N7-MeGua and a cumulative increase with the dacarbazine dose compared to the other two patients. For several patients adduct levels were monitored during two chemotherapy cycles, for which quite similar data were obtained.
van Delft
J H
JH
TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
van den Ende
A M
AM
Keizer
H J
HJ
Ouwerkerk
J
J
Baan
R A
RA
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004247:DNA / Q000097:blood*; D003606:Dacarbazine / Q000008:administration & dosage / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy*; D008875:Middle Aged; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy*
D006147:Guanine; C008450:7-methylguanine; D003606:Dacarbazine; D004247:DNA