Increased growth adaptability to 5-fluorouracil and methotrexate of HT-29 sub-populations selected for their commitment to differentiation
✍ Scribed by Thécla Lesuffleur; Anne Kornowski; Chantal Augeron; Elisabeth Dussaulx; Alain Barbat; Christian Laboisse; Alain Zweibaum
- Book ID
- 102864177
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- French
- Weight
- 928 KB
- Volume
- 49
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Adaptation of the heterogeneous human colon carcinoma cell line HT-29 to lethal concentrations of methotrexate (MTX) and 5-fluorouracil (FUra) was shown to result in the emergence of sub-populations of cells all stably committed to differentiation. It was postulated that these populations result from selection of a few cells present in the parental line which possess, associated with their ability to differentiate, particular advantages allowing them to adapt to adverse conditions such as MTX or FUra. The purpose of the present study was to further verify this hypothesis by investigating whether HT-29 sub-populations selected for the commitment of all cells t o differentiation would spontaneously be more resistant and adaptable than the parental cells to MTX and FUra. This study included a mucus-secreting clone (HT29-I6E), a transporting clone (HT29-I 9A), and an enterocytic population selected by glucose deprivation (HT29-Glc-'+).
Although all 3 populations show only a slight increase in their spontaneous resistance to both drugs, as substantiated by the values of IC,, which are only less than 2-fold higher than in parental cells, they are more adaptable as judged by growth curves, over a 50-day culture period, under exposure to I pM FUra and 0.1 p~ MTX. In sharp contrast to parental cells, which, at these concentrations, show a high rate of mortality, all