Ionising radiation and childhood leukaemia revisited

ABSTRACT

Increased incidences of childhood acute leukaemia were noted among survivors of the atomic bombings of Hiroshima and Nagasaki. In Western societies, Childhood Acute Lymphoblastic Leukaemia has a distinct epidemiology peaking at 3 years old. Exposure to ionising radiation is an established hazard but it is difficult to gauge the precise risk of less than 100 mSv. Since 1983 significant leukaemia incidences have been reported among families residing near nuclear installations. The target cells (naïve neonatal lymphocytes) get exposed to multiple xenobiotic challenges and undergo extraordinary proliferation and physiological somatic genetic change. Population movements and ionising radiation are considered taking account of updated understanding of radiation biology, cancer cytogenetics and immunological diversity. Double Strand Breaks in DNA arise through metabolic generation of Reactive Oxygen Species, and nearly always are repaired; but mis-repairs can be oncogenic. Recombinant Activating Gene enzymes in rapidly dividing perinatal pre-B lymphocytes being primed for antibody diversity are targeted to Signal Sequences in the Immunoglobulin genes. off target pseudo-sequences may allow RAG enzymes to create autosomal DSBs which, when mis-repaired, become translocated oncogenes. Immunogens acting by chance at crucial stages may facilitate this. In such circumstances, oncogenic DSBs from ionising radiation are less likely to be significant.

KEYWORDS:

• Childhood leukaemia
• ionising radiation
• immuno-cytogenetics
• population mixing
• two-hit hypothesis

Acknowledgments

I have had helpful discussions with various colleagues within Medact, IPPNW and former colleagues in haemato-oncology, but I am solely responsible for the views expressed in this review.

Disclosure statement

No potential conflict of interest was reported by the author.

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Frank Boulton

Frank Boulton MD. Retired physician, specialty haematology and haemato-oncology. Member of Medact – past Board Member and Chair. Held Consultant and academic posts in major teaching hospitals at the Royal London Hospital, Liverpool Royal Infirmary, Edinburgh Royal Infirmary and SE Scotland Blood Transfusion Service, Southampton General Hospital and Wessex Regional Blood Transfusion Service and National Blood and Transplant, England. Past President British Blood Transfusion Society.