Delayed chromosomal instability in lymphocytes of cancer patients after radiotherapy

Abstract

Purpose: To assess possible delayed chromosomal instability (DCI) expressed as elevated chromatid breakage in cells containing previously formed chromosome type aberrations in cultured blood lymphocytes of cancer patients after radiotherapy (RT).

Materials and methods: Twenty patients treated for uterine cancer with external Co⁶⁰ RT, without chemotherapy, were selected. Blood was taken before, 1–2 days after RT and one year later. Lymphocytes were cultured for 50 and 100 h. Metaphases were stained with fluorescence-plus-Giemsa and analysed for chromosome and chromatid aberrations in 1st (M1) and 3rd plus later (M3+) mitoses.

Results: RT caused a significant increase of radiation-specific chromosome aberrations in patients' lymphocytes together with DCI, which was observed as an excessive yield of cells containing both chromosome and chromatid aberrations (defined as C_acs&act). This DCI passed successfully through mitoses in vitro, and at the end of RT a mean yield of ‘extra’ C_acs&act was 3 × 10⁻³ × cell⁻¹ amongst either M1 or M3+ cells. At the end of RT and one year later DCI in M1 lymphocytes appeared at random amongst patients, but some inter-individual variation was found for DCI presence in M3+ cells at both post-irradiation samplings. As time passed, the mean yield of lymphocytes exhibiting DCI decreased in vivo and one year after RT reached the pre-treatment level of 1 × 10⁻³ × cell⁻¹.

Conclusions: DCI was demonstrated in descendants of human lymphocytes after therapeutic irradiation. The effect diminished one year later, suggesting that the progeny of patients' irradiated stem cells did not produce new daughter lymphocytes exhibiting DCI during the studied post-irradiation period.

Keywords:

• chromosomal instability
• radiotherapy
• chromosome aberrations
• uterine cancer
• bystander effects
• chromatid aberrations

Acknowledgements

The work was carried out as a part of two projects (AMN 02.05 and AMN 02.08) of the Academy of Medical Science of Ukraine. V.A.V. was supported by a Young Scientist Fellowship from the International Association for the promotion of cooperation with scientists from the New Independent States of the former Soviet Union (INTAS YS 05-109-46-43). The authors would like to thank Dr Elizabeth Ainsbury of the UK Health Protection Agency for the discussion of statistical issues in this research.

Declaration of interest: The authors have no conflicts of interest. They alone are responsible for the content and writing of the paper.