Evidence for acrolein-modified DNA in peripheral blood leukocytes of cancer patients treated with cyclophosphamide.
Monitoring human populations for specific DNA modifications has been made possible by developing highly sensitive immunoassays employing antibodies specific for carcinogen-DNA adducts. While these techniques have been used to follow occupationally and environmentally exposed populations, results have been limited by the lack of exposure data with which to correlate adduct formation. Cancer patients treated with precisely known doses of anticancer drugs can be studied to examine the association between drug dose and adduct formation. This study examined acrolein-modified DNA in patients treated with the anticancer drug cyclophosphamide (CP) and in newly diagnosed patients prior to treatment. Employing 2 different detection methods, enzyme-linked immunosorbent assay (ELISA) and immuno-dot blot (IDB), acrolein-modified DNA was identified in a total of 6 of 12 (50%) treated patients and in 0 of 15 untreated patients. Formation of acrolein-modified DNA was examined as a function of lifetime CP dose, recent CP dose, time since last treatment, regime of treatment, and smoking history; however no clear trends were observed.
McDiarmid
M A
MA
Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205.
Iype
P T
PT
Kolodner
K
K
Jacobson-Kram
D
D
Strickland
P T
PT
D000171:Acrolein / Q000494:pharmacology*; D000328:Adult; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D012907:Smoking; D013997:Time Factors
D014408:Biomarkers, Tumor; D000171:Acrolein; D003520:Cyclophosphamide; D004247:DNA