Effect of glucocorticoid hormones in vitro on the structural integrity of nuclei in corticosteroid-sensitive and -resistant lines of lymphosarcoma P1798.
Exposure of rat thymus cells to glucocorticoids leads to a decreased ability of nuclei to survive the lysis of whole cells by hypotonic shock. In this study, a similar glucocorticoid-induced increase in "nuclear fragility" was found in both corticoid-sensitive and -resistant lines of P1798 mouse lymphosarcoma cells. In corticoid-sensitive cells a small increase in nuclear fragility is seen after a 2-hr exposure to cortisol (10(-6) M); by 3 hr it is 20 to 40% above control values. This effect appears to be a specific glucocorticoid response. Both cortisol and dexamethasone at 10(-7) M produce an effect, 10(-6) M testosterone is inactive, and cortexolone, which binds to glucocorticoid receptors, reduces the effect. Cycloheximide, at concentrations that inhibit protein synthesis, also blocks this effect. While the corticoid-resistant line also demonstrates an effect of similar magnitude, it requires a much longer exposure to the hormone (6 hr). Distinct differences in the "hardiness" of the two cell lines (nuclei of the corticoid-resistant line are less fragile) measurable in the absence of hormones appears to account for the differential susceptibility to steroids. On this basis a new theory of resistance is advanced where the emergence of resistance is related to structural differences in the cells.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003350:Cortodoxone / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D003907:Dexamethasone; D003513:Cycloheximide; D003350:Cortodoxone; D006854:Hydrocortisone