Metabolic restriction of cancer cells in vitro causes karyotype contraction--an indicator of cancer promotion?

The metabolism of cultured cancer cells is stimulated by 21% oxygen and generous nutrition, while real tumors grow in oxygen and nutrient-restricted environments. The effect of these contrasted conditions was studied in five hyperploid (54-69) cancer cell lines. When grown under anoxia and in the presence of antioxidant metabolic restrictors, the cell lines quickly reverted to almost normal chromosome numbers (47-49). The stepped withdrawal of oxygen over K562 showed progressive increases in proliferation rate and the acquisition of a stable, stem phenotype. In genetic studies, hyperploid cancer cells adjusted their chromosome numbers up or down to match their micro-environment through rapid mechanisms of endo-reduplication or chromosome loss. These fast reactions may explain the surprising adaptability of tumor cells to oncologic interventions. Furthermore, karyotype contraction may provide a basis for the previously observed carcinogenic influence of the administration of some antioxidants in human populations.