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

Abstract

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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