Abstract
DNA adduct levels were measured with atomic spectroscopy in white blood cells (WBCs) from patients with solid tumours who were treated with six weekly courses of cisplatin. In 21 patients (I) the WBCs were collected after thawing frozen whole-blood samples according to a previously described method. In 32 other patients (II) WBCs were collected immediately after blood sample collection. The two methods for WBC collection were also compared in vitro. The maximal DNA adduct levels in vivo after the first course were in I 2.48 +/- 1.14 and in II 1.28 +/- 0.40 pg of platinum per microgram of DNA (P < 0.0001). The DNA 'repair' in the first course (DNA adduct level at the end of the infusion minus the level 15 h post infusion) was in I 40% +/- 29% and in II 18% +/- 29% (P = 0.009). These differences were consistent in all measured courses. In vitro, the DNA adduct levels in the freshly prepared WBCs were significantly lower at 0, 1 and 4, but not 24 h, after start of the incubation with cisplatin than in the WBCs collected after freezing and thawing the blood sample. The same experiment with carboplatin in vitro also resulted in significantly lower adducts in freshly isolated WBCs. The higher DNA adduct levels and DNA 'repair' in I are caused by remaining unbound cisplatin in the sample tubes, which can form DNA adducts ex vivo. The same results in vivo can be anticipated when carboplatin is used.
Highlights
Su_manr DNA adduct levels were measured with atomic spectroscopy in white blood cells (WBCs) from patients with sold tumours who were treated with six weekly courses of cisplatin
We describe the two procedures and the influence on the quantitation of the DNA adduct levels in vivo
The sampling times in these patients were at baseline and at 0, 1, 2, 5 and 15h after the end of the 3h infusion of Collection of WBCs from frozen whole blood samples This method is described by Fichtinger-Schepman et al (1987)
Summary
All patients gave informed consent according to local regulatory requirements. Eligibility for the clinical study required a pathologically confirmed mesothelioma, melanoma, non-small-cell lung cancer, colon cancer, adenocarcinoma of unknown primary or H/N cancer. Each patient had a complete medical history taken and underwent a physical examination, complete blood count, platelet count and serum tests. All patients had adequate renal and liver function, i.e. serum creatinine
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have