EFFECT OF GLUCOCORTICOID HORMONES INVITRO ON STRUCTURAL INTEGRITY OF NUCLEI IN CORTICOSTEROID-SENSITIVE AND CORTICOSTEROID-RESISTANT LINES OF LYMPHOSARCOMA P1798

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (11) , 3673-3680
Abstract
Exposure of rat thymus cells to glucocorticoids leads to a decreased ability of nuclei to survive the lysis of whole cells by hypotonic shock. A similar glucocorticoid-induced increase in nuclear fragility was found in corticoid-sensitive and -resistant lines of P1798 mouse lymphosarcoma cells. In corticoid-sensitive cells a small increase in nuclear fragility was seen after a 2 h exposure to cortisol (10-6 M); by 3 h it was 20-40% above control values. This effect appeared to be a specific glucocorticoid response. Cortisol and dexamethasone at 10-7 M produced an effect, 10-6 M testosterone was inactive and cortexolone, which binds to glucocorticoid receptors, reduced the effect. Cycloheximide, at concentrations that inhibit protein synthesis, also blocked this effect. While the corticoid-resistant line demonstrated an effect of similar magnitude, it required a much longer exposure to the hormone (6 h). Distinct differences in the hardiness of the 2 cell lines (nuclei of the corticoid-resistant line were less fragile) measurable in the absence of hormones appears to account for the differential susceptibility to steroids. A new theory of resistance was advanced where the emergence of resistance was related to structural differences in the cells.

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