Cytogenetic damage in lymphocytes of patients undergoing therapy for small cell lung cancer and ovarian carcinoma

Toxicol Appl Pharmacol. 2005 Dec 1;209(2):183-91. doi: 10.1016/j.taap.2005.04.005.

Abstract

The level of cytogenetic damage in peripheral blood lymphocytes of patients undergoing chemotherapy has been analyzed incisively 20 years ago. The results showed that the highest level of cytogenetic damage was observed at the end of therapy. In recent years, the doses of anticancer drugs were intensified thanks to the discovery of colony stimulating factors. Therefore, it was interesting to analyze the kinetics of micronuclei formation in lymphocytes of patients undergoing modern chemotherapy. The frequencies of micronuclei were measured in lymphocytes of 6 patients with small cell lung cancer treated with a combination of cisplatin and etoposide and 7 patients with ovarian carcinoma treated with a combination of taxol and cisplatin. 3 patients with lung cancer received radiotherapy in addition to chemotherapy. Micronuclei were analyzed in lymphocytes collected before the start of therapy and 1 day before each following cycle of chemotherapy. The micronucleus frequencies were compared with the kinetics of leukocyte counts. The micronucleus frequencies showed an interindividual variability. On average, the frequencies of micronuclei increased during the first half of therapy and declined thereafter, reaching, in some patients with ovarian carcinoma, values below the pre-treatment level. Leukocyte counts decreased strongly at the beginning of therapy with an upward trend at the end. We suggest that the decline of micronuclei was due to repopulation of lymphocytes and acquired drug resistance.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Small Cell / blood*
  • Carcinoma, Small Cell / drug therapy
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Dose-Response Relationship, Drug
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Humans
  • Kinetics
  • Leukocyte Count
  • Lung Neoplasms / blood*
  • Lung Neoplasms / drug therapy
  • Lymphocytes / drug effects*
  • Male
  • Micronuclei, Chromosome-Defective / chemically induced*
  • Micronucleus Tests
  • Middle Aged
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / drug therapy
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects

Substances

  • Etoposide
  • Paclitaxel
  • Cisplatin