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CHROMOSOME ABERRATIONS

Chromosome aberrations are prospective indicators of cancer risk.

  • Breaks (chromatid or chromosome)
  • Deletion
  • Translocation
  • Duplication
  • Circularisation
  • Dicentrics (two centromeres on one chromosome)
  • Quadri-radials
http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/chromosomaberrations.JPG

Figure Examples of chromosome aberrations.

Chromosome aberrations (CA) were recorded for 3182 subjects in a Nordic cohort study of cancer incidence between 1970 and 1991. Subjects were classified as having low, medium or high CA frequency (percentile ranges 1-33, 34-66, 67-100). 85 cases of cancer were diagnosed between 1970 and 1991. There was a significant trend (P<0.001) associating CA frequency with cancer risk. Thus, an increased level of CA seems to be a relevant biomarker of future cancer risk. Similar findings from Italian and Czech cohorts. Perhaps surprisingly, chromosome aberrations here were strongly influenced by exposure.

Many aberrations lead to loss of genetic material in one of the daughter cells, or may disrupt division itself and lead to cellular dysfunction or death.
Translocations tend not to involve loss and so are stably transmitted through generations of cells.
They can be detected by 'chromosome painting'.
Translocated genes may have altered regulation of expression. The so-called 'Philadelphia chromosome' - Wikipedia is present in the cancer cells of all patients with chronic myelocytic leukaemia. The c-abl proto-oncogene is transposed from chr. 9 to chr. 22 where it is abnormally transcribed and gives rise to a fusion protein with oncogenic properties.

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/translocations.JPG

Figure Three translocations between chromosome 1 and unpainted chromosomes (thanks to Radim Sram, Prague).

Chromosome aberrations and antioxidants

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/chromosomaberrations3.JPG

Figure Antioxidant supplementation and chromosome aberrations in lymphocytes.

Volunteers were given a daily supplement of vitamin C, vitamin E, beta-carotene and Se (see figure above). Chromosome aberrations were scored in stimulated lymphocytes. The % of aberrant cells and the chromatid break frequency were lower after antioxidants.