Somatic mutations at the T-cell antigen receptor in antineoplastic drug-exposed populations: comparison with sister
A Lanza1, F S Robustelli della Cuna, C Zibera
1Divisione di Oncologia Medica IRCCS Fondazione "S. Maugeri", Via Ferrata 8, I-27100 Pavia, Italy. alanza@fsm.it
Objective:
The objective of this study was to assess the genetic effect of occupational exposure to antineoplastic agents.
Method:
The influence of occupational handling of cytotoxic drugs was investigated by monitoring the frequency of sister chromatid exchanges (SCE), the percentage of cells with high frequencies of SCE (high-frequency cells, HFC), and the frequency of somatic mutation at the T-cell receptor (TCR) locus in mononuclear cells of exposed hospital nurses. These parameters were also measured in healthy donors and in cancer patients at the time of the diagnosis and following the administration of high doses of cytotoxic drugs requiring stem cell support.
Results:
Our results show that (a) SCE and HFC values in occupationally exposed nurses do not differ from controls, (b) patients with newly diagnosed cancer or following chemotherapy show a number of SCE comparable to those of healthy donors, but a significantly different percentage of HFC, (c) cigarette smokers of all categories studied show higher frequencies of SCE and HFC as compared to nonsmokers, but the differences are not statistically significant, (d) the mutation frequency at the TCR locus in oncology nurses is higher, but not significantly different from the frequency in the control group, and (e) the increase of mutation frequency is statistically significant and seems to be dose dependent in patients treated with high-dose chemotherapy.
Conclusions:
Our data suggest that SCE frequency and HFC percentage are not reliable indicators of exposure to possible mutagenic/carcinogenic effects of antineoplastic drugs; on the contrary, our observations indicate that anticancer therapy induces somatic mutations at the TCR locus and suggest an association between exposure to cytotoxic agents and the increase in somatic mutations.
Insights
Occupational exposure to antineoplastic drugs did not alter sister chromatid exchange (SCE) or high-frequency cells (HFC). However, anticancer therapy significantly increases somatic mutations at the T-cell receptor (TCR) locus.
Area of Science:
- Genetics
- Occupational Health
- Toxicology
Background:
- Occupational exposure to antineoplastic agents in healthcare settings is a concern.
- Assessing the genotoxic effects of these agents is crucial for worker safety.
Purpose of the Study:
- To evaluate the genetic impact of occupational exposure to antineoplastic drugs on hospital nurses.
- To compare genotoxicity markers in exposed nurses, healthy donors, and cancer patients undergoing chemotherapy.
Main Methods:
- Monitored sister chromatid exchanges (SCE) and high-frequency cells (HFC) in mononuclear cells.
- Assessed somatic mutation frequency at the T-cell receptor (TCR) locus.
- Compared exposed nurses to healthy controls and cancer patients.
Main Results:
- No significant difference in SCE or HFC was found between occupationally exposed nurses and controls.
- Cancer patients undergoing chemotherapy showed a significantly different percentage of HFC.
- Somatic mutation frequency at the TCR locus was higher in oncology nurses but not significantly different from controls.
- A statistically significant, dose-dependent increase in mutation frequency was observed in patients treated with high-dose chemotherapy.
Conclusions:
- Sister chromatid exchange (SCE) and high-frequency cells (HFC) are not reliable biomarkers for antineoplastic drug exposure.
- Anticancer therapy demonstrably induces somatic mutations at the TCR locus.
- Cytotoxic agent exposure is associated with an increased rate of somatic mutations.
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