Acute cytogenetic effects of antineoplastic drugs on peripheral blood lymphocytes in cancer patients chromosome aberrations and micronuclei.
OBJECTIVE
The aim of the present study was to evaluate the individual sensitivity of cancer patients to different antineoplastic drugs administered in standard protocols by assessing their acute cytogenetic effects on peripheral blood lymphocytes.


METHODS
In 12 patients undergoing cancer chemotherapy, acute cytogenetic effects on peripheral blood lymphocytes were evaluated by analysis of structural chromosome aberrations and micronuclei. All patients were given antineoplastic drugs, mainly as polychemotherapy. The frequencies of both cytogenetic biomarkers determined after the first chemotherapy cycle were compared with their pre-treatment (baseline) values.


RESULTS
All chemotherapy protocols employed induced clear cytogenetic effects in both tests studied. The results obtained indicate interindividual variations between cytogenetic damage in peripheral blood lymphocytes among cancer patients. Statistically significant increases in the total number of structural chromosome aberrations and micronuclei in lymphocytes analyzed after chemotherapy compared to pre-therapy samples were observed in almost all patients studied. The highest level of chromosome damage as well as the highest incidence of micronuclei was observed following administration of the ACOP protocol (adriamycin, cyclophosphamide and vincristine). The proportions of signal-positive and signal-negative micronuclei were evaluated using DAPI staining, while silver staining revealed Ag-NOR+ and Ag-NOR- micronuclei. In some patients the incidence of signal-positive and Ag-NOR+ micronuclei after treatment was increased, indicating a more pronounced susceptibility of particular chromosomes to damage caused by antineoplastic drugs.


CONCLUSIONS
With regard to the results obtained we may conclude that both parameters used in the present study on peripheral lymphocytes are sensitive biomarkers and can be successfully employed for biomonitoring of acute cytogenetic effects induced by antineoplastic drugs in standard clinical protocols for cancer treatment.
Kopjar
Nevenka
N
Laboratory of Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia. nkopjar@imi.hr
Garaj-Vrhovac
Vera
V
Milas
Ivan
I
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001399:Azure Stains; D015415:Biomarkers; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D007211:Indoles; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D016622:Silver Staining / Q000379:methods; D013194:Staining and Labeling / Q000379:methods
D000970:Antineoplastic Agents; D001399:Azure Stains; D015415:Biomarkers; D007211:Indoles; C007293:DAPI