Loss of several cell functions including okadaic acid-induced apoptosis after multiple passages in FRTL-5 cells

In FRTL-5 cells, cultured over a period of more than 3 years, different pro perties of the cells have been observed to undergo spontaneous changes in t he course of aging, i.e. after an increase in the number of passages. This consists mainly in alterations in their morphological phenotype and in some of their functional properties. The morphology of the cells displayed a pr ogressive disruption of the monolayer organization with a loss of cell-cell contacts and a marked rounding-up of the cells. The uptake of iodide was n ot modified nor was the expression of thyroglobulin (Tg) mRNA as determined at various time intervals in the course of the cells culturing. Estimation of the proliferation by counting the frequency of [H-3]thymidine labeled n uclei revealed an age-related decline in the sensitivity to TSH mitogenic a ction associated with a reciprocal increase in the insulin synergistic effe ct. Aged cells (+/-40 passages) lost their apoptosis sensitivity to the pho sphatase inhibitor, okadaic acid (OA) but not to cycloheximide (CHX) and/or actinomycin D (act. D) exposure. Altogether these observations favor the e xistence of a shift towards transformed properties with only partial loss o f differentiated functions. (C) 1999 Elsevier Science Ireland Ltd. All righ ts reserved.