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Life Span Study

Investigating the relative biological effectiveness of ingested tritium vs exposure to Co-60 gamma rays on the tumorigenesis and latency in mice.
Life Span Study

Experimental Design

The study started in February 2012 and completed in July 2020, encompassing more than eight years of mouse work. Three thousand six hundred and nineteen female CBA/CaJ mice, aged 8 weeks, were microchipped, and allocated to one of five dose groups. There were 9 cohorts, including two exposure types, external Cobalt-60 open beam and internally via tritiated drinking water (as HTO or organically bound [OBT]). Irradiations were continuous for 14 days and the doses delivered were confirmed using TLD dosimeters (for the external gamma). All the doses delivered at a dose rate below 6mGy/h.

Following irradiation, the mice were provided with food and water ad libitum. The health status of the mice was monitored and any judged to be terminally sick were euthanized.
Ten tissues, plus any observed abnormalities, were excised, fixed in formalin, embedded in paraffin wax, and sectioned for histopathology. A database was created listing the time to death and pathologies found for each mouse. This was used to create survival and tumour profile data for each dose cohort. Analyses of the data was undertaken to investigate differences in survival and tumour profiles between the exposed and control cohorts.

Summary of the cohorts:


Co-60 Gamma (mGy):

  • 69
  • 255
  • 565
  • 1599

Tritium (MBq/L)

  • 150
  • 500
  • 1200
  • 3000

The total absorbed doses were matched (per line) for each exposure type.

All mice were allowed to live for their natural lifespan, although most were euthanized when moribund or for humane reasons and to prevent autolysis which can rapidly cause tissues to degrade and compromise the accurate diagnosis of lesions. Some mice in this investigation died before euthanasia; autolysis was noted and recorded. Euthanasia was by isoflurane deep anaesthesia followed by cervical dislocation.

All mice had a documented clinical history (via database), and each was subjected to a full necropsy with all macroscopically observed lesions reported. At necropsy the tissues were routinely sampled and fixed in 10% neutral buffered formalin.

Tissues available:

  • Lung – all lobes
  • Liver – all lobes
  • Spleen
  • Adrenal glands
  • Kidneys
  • Ovaries
  • Uterus
  • Bone and marrow (femur)
  • Any macroscopically observed lesions

Fixed tissues were processed to paraffin wax, sectioned at 5µm and stained with haematoxylin and eosin. Additional stains were employed as required. The remaining tissues (and carcass) were preserved in formalin but not further dissected or processed). All wax blocks, slides, and formalized tissues are available. Additionally, all neoplastic lesions were recorded by tissue and type on an Excel spreadsheet.

The CNL Tissue Bank has a collection of approximately 33,000 individual tissue samples from this study. Main Database with Histopathology Reports.